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The goal of this narrative review is to summarize the effects of prolonged fasting on various metabolic health measures, including body weight, blood pressure, plasma lipids, and glycemic control. Prolonged fasting is characterized by consciously eating little to no food or caloric beverages for several days to weeks. Results reveal that prolonged fasting for 5–20 days produces potent increases in circulating ketones, and mild to moderate weight loss of 2–10%. Approximately two-thirds of the weight lost is lean mass, and one-third is fat mass. The excessive lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern. Systolic and diastolic blood pressure consistently decreased with prolonged fasting. However, the impact of these protocols on plasma lipids is less clear. While some trials demonstrate decreases in LDL cholesterol and triglycerides, others show no benefit. With regard to glycemic control, reductions in fasting glucose, fasting insulin, insulin resistance, and glycated hemoglobin (HbA1c) were noted in adults with normoglycemia. In contrast, these glucoregulatory factors remained unchanged in patients with type 1 or type 2 diabetes. The effects of refeeding were also examined in a few trials. It was shown that 3–4 months after the fast was completed, all metabolic benefits were no longer observed, even when weight loss was maintained. With regard to adverse events, metabolic acidosis, headaches, insomnia, and hunger were observed in some studies. In summary, prolonged fasting appears to be a moderately safe diet therapy that can produce clinically significant weight loss (>5%) over a few days or weeks. However, the ability of these protocols to produce sustained improvements in metabolic markers warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Lower skeletal muscle mitochondrial function is associated with future cognitive impairment and mobility decline, but the biological underpinnings for these associations are unclear. We examined metabolomic markers underlying skeletal muscle mitochondrial function, cognition and motor function. Methods We analysed data from 560 participants from the Baltimore Longitudinal Study of Aging (mean age: 68.4 years, 56% women, 28% Black) who had data on skeletal muscle oxidative capacity (post-exercise recovery rate of phosphocreatine, kPCr) via 31P magnetic resonance spectroscopy and targeted plasma metabolomics using LASSO model. We then examined which kPCr-related markers were also associated with cognition and motor function in a larger sample (n = 918, mean age: 69.4, 55% women, 27% Black). Results The LASSO model revealed 24 metabolites significantly predicting kPCr, with the top 5 being asymmetric dimethylarginine, lactic acid, lysophosphatidylcholine a C18:1, indoleacetic acid and triacylglyceride (17:1_34:3), also significant in multivariable linear regression. The kPCr metabolite score was associated with cognitive or motor function, with 2.5-minute usual gait speed showing the strongest association (r = 0.182). Five lipids (lysophosphatidylcholine a C18:1, phosphatidylcholine ae C42:3, cholesteryl ester 18:1, sphingomyelin C26:0, octadecenoic acid) and 2 amino acids (leucine, cystine) were associated with both cognitive and motor function measures. Conclusion Our findings add evidence to the hypothesis that mitochondrial function is implicated in the pathogenesis of cognitive and physical decline with aging and suggest that targeting specific metabolites may prevent cognitive and mobility decline through their effects on mitochondria. Future omics studies are warranted to confirm these findings and explore mechanisms underlying mitochondrial dysfunction in aging phenotypes. [ABSTRACT FROM AUTHOR]

Background Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors. Methods Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls. Results Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy. Conclusions Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population. [ABSTRACT FROM AUTHOR]

Context Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25–30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis. Objective The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters. Data Sources Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980). Data Extraction A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD. Results The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: –76.93, –12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05). Conclusion Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations. Systematic Review Registration PROSPERO registration no. CRD42021251980. [ABSTRACT FROM AUTHOR]

Context Cardiovascular disease is the leading cause of death worldwide. Low-calorie, low-fat therapeutic diets (TDs) developed by the US National Cholesterol Education Program, ie, the Step I and II diets and the therapeutic lifestyle changes diet, are approximately similar and are the initial therapeutic interventional approaches for lifestyle modification. Objective This systematic review with meta-analysis was undertaken to evaluate the effects of TDs diet on blood lipids, apolipoprotein A-1, apolipoprotein B, blood pressure, fasting blood glucose, and insulin. Data Sources A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases until October 2022 was performed to identify clinical trials investigating the effects of TDs on the aforementioned parameters. Data Extraction One investigator screened the records and extracted data, and another reviewed the extracted data. Data Analysis A total of 910 records were retrieved. After records were screened for eligibility, 34 clinical trials met the inclusion criteria. The pooled analysis from the random-effects model revealed a significant reduction in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1, and apolipoprotein B in the TD intervention group vs the control group. The overall effects of TDs on fasting blood glucose, insulin, and blood pressure were not significant, but the results of subgroup analysis revealed a significant reduction in fasting blood glucose with the Step II diet and an intervention duration of more than 24 weeks. For blood pressure, the Step I diet and an intervention duration of more than 24 weeks resulted in significant reduction. There was no evidence of publication bias, but strong heterogeneity was observed. Conclusion Therapeutic diets have promising effects on lipid profile parameters, glycemic indexes, and blood pressure, which can promote cardiovascular health. Systematic Review Registration PROSPERO registration no. CRD42021259355. [ABSTRACT FROM AUTHOR]

Context A recent US national survey of the health status of the male transgender population has raised awareness about the little-studied relationship between testosterone hormone therapy in transgender men and cardiovascular outcomes. Objective The aim of this systematic review was to assess the relationship between cross-sex hormone therapy in transgender men and lipid profiles and cardiovascular risk. Data Sources The PubMed, SciELO, SpringerLink, and EBSCOhost databases were searched up to March 2021 for studies assessing the association between cross-sex hormone therapy and the incidence of outcomes related to cardiovascular disease in transgender men over 18 years of age. Data Extraction Data extracted were sorted into clinical data (systolic, diastolic, and mean blood pressure), anthropometric data (body mass index, weight, waist circumference, fat mass, and lean mass), and biochemical data (triglycerides, total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], very low-density lipoprotein cholesterol [VLDL-C], and the HDL-C to LDL-C ratio). Data Analysis Study quality was appraised independently by two reviewers using the Cochrane tools for assessment of methodological quality or risk of bias in nonrandomized studies, and the Newcastle-Ottawa Scale was applied. Of 735 studies identified, 11 were included in the review. Most studies reported no change in cholesterol or triglyceride levels after hormone treatment. A reduction in HDL-C levels was observed in 7 of 11 studies, although this alone cannot be considered a cardiovascular risk factor. Likewise, clinical and anthropometric findings showed no changes predictive of cardiovascular risk. Conclusions Although these findings suggest that hormone therapy may lead to a decrease in HDL-C levels and an increase in LDL-C levels, they are insufficient to establish a relationship with cardiovascular disease. Furthermore, no significant effects on metabolic and anthropometric values were found. Further studies with higher quality and longer follow-up periods are needed to establish cardiovascular risk. Systematic Review Registration PROSPERO registration number CRD 42020212560. [ABSTRACT FROM AUTHOR]

Variability in sleep duration and cardiovascular health have been infrequently investigated, particularly among reproductive-age women. We examined these associations across the menstrual cycle among a cohort of 250 healthy premenopausal women, aged 18-44 years. The BioCycle study (New York, 2005–2007) collected cardiovascular biomarkers (serum high- and low-density lipoprotein (HDL, LDL), total cholesterol, triglycerides, and C-reactive protein (CRP)) at key time points along the menstrual cycle (follicular, ovulatory, and luteal phases). Women also recorded sleep duration in daily diaries. From these data, we computed L-moments, robust versions of location, dispersion, skewness, and kurtosis. We fitted linear mixed models with random intercepts and inverse probability weighting to estimate associations between sleep variability and cardiovascular biomarkers, accounting for demographic, lifestyle, health, and reproductive factors. Sleep dispersion (any deviation from mean duration) was associated with lower mean LDL for nonshift workers and non-White women. Skewed sleep duration was associated with higher mean CRP and lower mean total cholesterol. Sleep durations with extreme short and long bouts (kurtosis) were associated with a lower mean HDL, but not mean CRP, LDL, or triglycerides. Sleep duration modified associations between sleep dispersion and LDL, HDL, and total cholesterol. Even in young and healthy women, sleep duration variability could influence cardiovascular health. [ABSTRACT FROM AUTHOR]

Aims: Psychological stress has been linked to lipid dysregulation with noticeable gender differences, but it remains unclear whether women are more susceptible to non-optimal lipid levels than men, when experiencing stressful life events. This study aims to examine the association between stressful life events and non-optimal lipid levels among persons with hyperlipidaemia and whether the association differs between men and women. Methods and results: A nested case–control study was performed using data from the Wisconsin Sleep Cohort (WSC) Study from 2011 to 2015, including 224 participants with hyperlipidaemia and without a history of myocardial infarction or heart failure. Among them, 63 participants with non-optimal LDL cholesterol or triglyceride levels were identified as cases, and 161 participants with optimal LDL cholesterol and triglyceride levels were identified as controls. Cases and controls were traced back to their self-reported life events collected through the Retirement and Sleep Trajectories study during 2010–11. The association between stressful life events and non-optimal lipid levels was examined using multivariable logistic regression; confounding effects were addressed using propensity score weighting and Mahalanobis distance matching; gender differences were examined using subgroup analysis. Results showed that a higher number of stressful life events during 2010–11 was associated with greater odds of non-optimal lipid levels during 2011–15 (odds ratio = 1.45, P = 0.03) among women with hyperlipidaemia, whereas the association was not significant among men with hyperlipidaemia (P = 0.910). Conclusion: Future studies are needed to examine the underlying mechanisms that explain gender differences in the association between stressful life events and non-optimal lipid levels. Registration: ClinicalTrials.gov NCT00005557 Graphical Abstract [ABSTRACT FROM AUTHOR]

Objectives Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1 * alleles and thrombosis in SLE. Conventional aPL were included for comparison. Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified. Results aPS/PT antibodies associated positively with HLA-DRB1 *13 [odds ratio (OR) 2.7, P  = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P  = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1 * alleles. HLA-DRB1*13 , but not DRB1*04 , remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03 , on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides. Conclusions HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk. [ABSTRACT FROM AUTHOR]

Background the effects regarding n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on sarcopenia have been explored by several clinical trials. Nonetheless, the use of n-3 PUFA for improving body composition, muscle strength and physical performance in older people is conflicting. Objectives our aim was to perform a randomised, double-blind, controlled trial to evaluate the effects of 6-month n-3 PUFA supplementation on body composition, muscle strength and physical performance in older Chinese people. Methods in this double-blind, placebo-controlled trial, 200 eligible subjects were randomly assigned to receive 4 g/day fish oil capsules (1.34 g eicosapentaenoic [EPA] + 1.07 docosahexaenoic [DHA]) or 4 g/day corn oil capsules (EPA + DHA <0.05 g) for 6 months. The primary outcomes were the changes of body composition, muscle strength (hand grip strength) and physical performance (Timed Up and Go time). Secondary outcomes were the changes in serum lipid profiles. Results compared with control group, fish oil-derived n-3 PUFA supplementation resulted in significant increases in thigh circumference (interaction time × group effect P  < 0.001), total skeletal muscle mass (interaction time × group effect P  < 0.001) and appendicular skeletal muscle mass (interaction time × group effect P  < 0.001); the differences were still significant even after height correction. Muscle strength and physical performance including hand grip strength (interaction time × group effect P  < 0.001) and Timed Up and Go time (interaction time × group effect P  < 0.001) were also improved after a 6-month fish oil-derived n-3 PUFA intervention. In terms of serum lipid profiles, fish oil-derived n-3 PUFA supplementation could significantly reduce serum level of triglyceride (interaction time × group effect P  = 0.012) and increase high density lipoprotein cholesterol (interaction time × group effect P  < 0.001); while no significant improvement was found in serum concentrations of total cholesterol (interaction time × group effect P  = 0.413) and low density lipoprotein cholesterol (interaction time × group effect P  = 0.089). Conclusions our present trial demonstrated that a 6-month fish oil-derived n-3 PUFA supplementation could beneficially affect the body composition, muscle strength, physical performance and serum lipid profiles in older people, which could be into considerations when making strategies aiming to the primary prevention of sarcopenia. [ABSTRACT FROM AUTHOR]

Many genetic risk factors for Parkinson's disease have lipid-related functions and lipid-modulating drugs such as statins may be protective against Parkinson's disease. Moreover, the hallmark Parkinson's disease pathological protein, α-synuclein, has lipid membrane function and pathways dysregulated in Parkinson's disease such as the endosome-lysosome system and synaptic signalling rely heavily on lipid dynamics. Despite the potential role for lipids in Parkinson's disease, most research to date has been protein-centric, with large-scale, untargeted serum and CSF lipidomic comparisons between genetic and idiopathic Parkinson's disease and neurotypical controls limited. In particular, the extent to which lipid dysregulation occurs in mutation carriers of one of the most common Parkinson's disease risk genes, LRRK2, is unclear. Further, the functional lipid pathways potentially dysregulated in idiopathic and LRRK2 mutation Parkinson's disease are underexplored. To better determine the extent of lipid dysregulation in Parkinson's disease, untargeted high-performance liquid chromatography-tandem mass spectrometry was performed on serum (n = 221) and CSF (n = 88) obtained from a multi-ethnic population from the Michael J. Fox Foundation LRRK2 Clinical Cohort Consortium. The cohort consisted of controls, asymptomatic LRRK2 G2019S carriers, LRRK2 G2019S carriers with Parkinson's disease and Parkinson's disease patients without a LRRK2 mutation. Age and sex were adjusted for in analyses where appropriate. Approximately 1000 serum lipid species per participant were analysed. The main serum lipids that distinguished both Parkinson's disease patients and LRRK2 mutation carriers from controls included species of ceramide, triacylglycerol, sphingomyelin, acylcarnitine, phosphatidylcholine and lysophosphatidylethanolamine. Significant alterations in sphingolipids and glycerolipids were also reflected in Parkinson's disease and LRRK2 mutation carrier CSF, although no correlations were observed between lipids identified in both serum and CSF. Pathway analysis of altered lipid species indicated that sphingolipid metabolism, insulin signalling and mitochondrial function were the major metabolic pathways dysregulated in Parkinson's disease. Importantly, these pathways were also found to be dysregulated in serum samples from a second Parkinson's disease cohort (n = 315). Results from this study demonstrate that dysregulated lipids in Parkinson's disease generally, and in LRRK2 mutation carriers, are from functionally and metabolically related pathways. These findings provide new insight into the extent of lipid dysfunction in Parkinson's disease and therapeutics manipulating these pathways may be beneficial for Parkinson's disease patients. Moreover, serum lipid profiles may be novel biomarkers for both genetic and idiopathic Parkinson's disease. [ABSTRACT FROM AUTHOR]

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n  = 311) and female (n  = 285) infants from the Santiago Longitudinal Study (1991–1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. Methods Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by ultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. Results In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. Conclusion We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients. [ABSTRACT FROM AUTHOR]

Background Blood lipids and glucose levels dysregulation represent potential mechanisms intermediating the adverse cardiovascular effects of ambient particulate matter (PM) exposure. This study aims to estimate the effect of long-term PM10 exposure on blood lipids and glucose levels and to assess the potential mediation and/or modification action of abdominal obesity (AO) (waist-to-height ratio). Methods Our study was based on 2,390 participants of the first Portuguese Health Examination Survey (INSEF, 2015) with available data on blood lipids and glucose parameters and living within a 30-km radius of an air quality monitoring station with available PM10 measurements. PM10 concentrations were acquired from the air quality monitoring network of the Portuguese Environment Agency. Generalized linear models were used to assess the effect of 1-year PM10 exposure on blood lipids and glucose levels. An interaction term was introduced in the models to test the modification action of AO. Results We found an association between PM10 and non-fasting blood triglycerides (TG) after adjustment for age, sex, education, occupation, lifestyles-related variables and temperature but only in participants with AO. Per each 1 µg/m3 PM10 increment, there was a 1.84% (95% confidence interval: 0.02–3.69) increase in TG. For the remaining blood lipid and glucose parameters, no associations were found. Conclusions Our study demonstrates that even at low levels of exposure, long-term PM10 exposure interacts with AO to increase blood TG. Our findings suggest that reducing both AO prevalence and PM10 below current standards would result in additional health benefits for the population. [ABSTRACT FROM AUTHOR]

Context There is renewed interest in using very low-carbohydrate ketogenic (VLCK) diets to manage diabetes. Many clinical trials have been published, often with mixed results. Objective This meta-analysis compares the effect of a VLCK diet on glycemic control, body weight, lipid profile, medication use, and dropouts with that of recommended diets for 12 weeks or longer in people with type 2 diabetes. Data Sources Ovid MEDLINE, Ovid Embase, CENTRAL, and CINAHL databases were searched (January 1980 through September 2019). Study Selection Two authors independently reviewed search results to select randomized controlled trials (RCTs) comparing a VLCK diet (carbohydrate intake < 50 g/d or < 10% of total energy) with any recommended diet for type 2 diabetes in adults. Discrepancies were resolved after consulting with the third author. Data Extraction Eight RCTs with 648 participants were identified. Results Compared with control diets, the VLCK diet resulted in a greater decrease in hemoglobin A1c after 3 months (weighted mean difference[WMD]: −6.7 mmol/mol; 95%CI, −9.0 to −4.4) (WMD: −0.61%; 95%CI, −0.82 to −0.40; P  < 0.001; moderate-certainty evidence) and after 6 months (WMD: −6.3 mmol/mol; 95%CI, −9.3 to −3.5) (WMD: −0.58%; 95%CI, −0.85 to −0.32; low-certainty evidence). There was a significantly greater weight loss with the VLCK diet after 3 months (WMD: −2.91 kg; 95%CI, −4.88 to −0.95; low-certainty evidence) and after 6 months (WMD: −2.84 kg; 95%CI, −5.29 to −0.39; low-certainty evidence). The VLCK diet was not better than a control diet after 12 months. It was superior in decreasing triglyceride levels, increasing high-density lipoprotein cholesterol levels, and reducing the use of antidiabetic medications for up to 12 months. Conclusion The VLCK diet appears to control glycemia and decrease body weight for up to 6 months in people with obesity and diabetes. Beneficial changes in serum triglycerides and high-density lipoprotein cholesterol, along with reductions in antidiabetic medications, continued in the VLCK group until 12 months. However, the quality of currently available evidence is not sufficient to recommend VLCK diets. A major limitation of the VLCK diet is patients' lack of adherence to carbohydrate restriction. Systematic Review Registration PROSPERO registration number CRD42020154700 [ABSTRACT FROM AUTHOR]

Context Consumption of lean fish and fish-derived proteins were effective for improving lipid profiles in published studies; however, evidence remains inconclusive. Objective To evaluate the effectiveness of lean fish or fish-derived protein on serum/plasma lipid and lipoprotein levels by conducting a systematic review of the literature and meta-analysis of available randomized controlled trials (RCTs). Data sources Medline (Ovid), Scopus, CINAHL, and Food and Nutritional Sciences databases were searched from the start date of each database to September 2019 to identify RCTs determining the effect of lean fish on lipid profile. Study selection Included RCTs investigated lean fish and fish-derived proteins intake and determined at least 1 major lipid or lipoprotein measurement. Data extraction Two reviewers independently evaluated 1217 studies against the inclusion and exclusion criteria. Relevant studies were assessed for risks of bias, and random-effects meta-analysis was conducted to generate average estimates of effect. Results A total of 24 studies met the inclusion criteria. Meta-analysis of data from 18 to 21 eligible crossover and parallel-design RCTs with a total of 1392 to 1456 participants found triacylglycerol-lowering effects for lean fish compared with no fish consumption. Lean fish intake showed no significant differences related to total cholesterol or lipoprotein levels. Subanalysis showed that parallel-group RCTs tended to find greater reduction effects on circulating triacylglycerol than did crossover RCTs. Conclusion Additional better-designed, longer, and larger RCTs, particularly crossover RCTs, are needed to clarify the impact of lean fish and fish proteins on the serum/plasma lipid profile. Findings from such studies would enable practitioners to provide their patients evidence-based recommendations to meet the American Heart Association guidelines for fish consumption to reduce cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Background: The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear.Methods: Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by the glomerular-filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys) and the urinary albumin-to-creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n = 331 368) and UK Biobank (n = 441 016), respectively, and kidney-function markers from the Trøndelag Health Study (HUNT; n = 69 736) and UK Biobank (n = 464 207). The reverse causal direction was examined using variants associated with kidney-function markers selected from recent genome-wide association studies.Results: There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney-function markers. Some, but inconsistent, evidence suggested a weak association of higher genetically predicted atherogenic lipid levels [indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B] with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels.Conclusion: Our MR estimates suggest that serum lipid and apolipoprotein levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels. [ABSTRACT FROM AUTHOR]

Aims Recent studies have emphasized that metabolic syndrome (MetS) was the most important modifiable risk factor for cardiovascular and cerebrovascular diseases in the institutionalized elderly. In addition, the occurrence of MetS was higher in those with longer age-adjusted institutionalization time. The present study was conducted to assess predictive value of markers of adipose tissue dysfunction for the early screening of MetS in this population. Methods and results Two hundred and eleven institutionalized older adults (132 women, aged 74.3 ± 7.3 years; 79 men, aged 71.5 ± 7.3 years) were enrolled in the current cross-sectional study. Lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), and triglycerides (TG)/high-density lipoprotein (HDL)-cholesterol ratio were determined. The receiver operating characteristic curve was calculated to compare the area under the curve of each index. The total prevalence of MetS was 23.8%. In female group, VAI and TG/HDL ratio presented moderate--high sensitivity (77.78% and 78.38%, respectively) and specificity (77.62% and 73.49%, respectively). In males group, LAP presented moderate--high sensitivity (75%) and specificity (76.9%). Conclusion Gender played a key role on the prediction of MetS by adipose dysfunction markers in institutionalized elderly. Accordingly, VAI and TG/HDL-cholesterol ratio showed the highest predictive value for MetS in female elderly. LAP was the strongest predictor of MetS in male elderly. [ABSTRACT FROM AUTHOR]

Aims Previous studies suggested that neck circumference (NC) as a new, simple, and valuable tool for the measuring obesity. However, the results of studies regarding the relationship between blood lipids and neck circumference were inconsistent. Therefore, we aimed to perform a systematic review and meta-analysis to summarize the association between NC and lipid profiles in adults. Methods and results PubMed and Scopus electronic databases were searched until 30 June 2018 to find articles that reported the association between NC and blood lipids. Mean serum lipids and variables contributed to heterogeneity were extracted. Sources of inter-study heterogeneity were determined by subgroup analysis. Of 2490 publications identi- fied, 33 studies were included in the qualitative and quantitative synthesis. We found an inverse correlation between NC and high-density lipoprotein cholesterol [HDL-C; overall Fisher's Z = -0.18; 95% confidence interval (CI): -0.21, -0.15]. Furthermore, we found positive associations between NC and total cholesterol (TC; overall Fisher's Z = 0.11; 95% CI = 0.06, 0.16), low-density lipoprotein cholesterol (LDL-C; overall Fisher's Z = 0.1; 95% CI = -0.04, 0.16), and triglyceride (TG; overall Fisher's Z = 0.21; 95% CI = 0.17, 0.25) in men. Neck circumference was directly correlated to TC (overall Fisher's Z = 0.1; 95% CI = 0.01, 0.19) and LDL-C (overall Fisher's Z = 0.16; 95% CI = 0.12, 0.20) in healthy and unhealthy women, respectively. There was no correlation between NC and serum concentration of TC (overall Fisher's Z = 0.01; 95% CI = -0.02, 0.03) and LDL-C (overall Fisher's Z = 0.09; 95% CI = 0.02, 0.16) in unhealthy and healthy women, respectively. Conclusion Higher NC in unhealthy men was strongly indirectly associated with HDL-C, and directly related to LDL-C, TG, and TC. In unhealthy women, higher NC was inversely associated with HDL and directly related to LDL-C. [ABSTRACT FROM AUTHOR]

Objective The relationship between serum lipid variations in SS and healthy controls was investigated to identify potential predictive lipid biomarkers. Methods Serum samples from 230 SS patients and 240 healthy controls were collected. The samples were analysed by ultrahigh-performance liquid chromatography coupled with Q Exactive™ spectrometry. Potential lipid biomarkers were screened through orthogonal projection to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis. Results A panel of three metabolites [phosphatidylcholine (18:0/22:5), triglyceride (16:0/18:0/18:1) and acylcarnitine (12:0)] was identified as a specific biomarker of SS. The receiver operating characteristic analysis showed that the panel had a sensitivity of 84.3% with a specificity of 74.8% in discriminating patients with SS from healthy controls. Conclusion Our approach successfully identified serum biomarkers associated with SS patients. The potential lipid biomarkers indicated that SS metabolic disturbance might be associated with oxidized lipids, fatty acid oxidation and energy metabolism. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear.Methods: Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64-407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium.Results: Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results.Conclusion: These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD. [ABSTRACT FROM AUTHOR]

Context Cardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required. Objective Carnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines. Data Sources The Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls. Data Extraction Basic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome. Data Analysis A total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n  = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], −0.32 mmol/L [95%CI, −0.57 to −0.07], P  = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, −0.14 mmol/L [95%CI, −0.20 to −0.08], P  < 0.001) compared with controls. In studies using carnosine, triglycerides levels were also lower in the intervention group vs controls (n = 5 RCTS; n = 309; P  < 0.001). There were no significant differences in blood pressure, heart rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) or the total cholesterol to HDL-C ratio between groups. Conclusions Carnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases. Systemic Review Registration PROSPERO registration no.: CRD42017075354 [ABSTRACT FROM AUTHOR]

Prevailing strategies in genome-wide association studies (GWAS) mostly rely on principles of medical genetics emphasizing one gene, one function, one phenotype concept. Here, we performed GWAS of blood lipids leveraging a new systemic concept emphasizing complexity of genetic predisposition to such phenotypes. We focused on total cholesterol, low- and high-density lipoprotein cholesterols, and triglycerides available for 29,902 individuals of European ancestry from seven independent studies, men and women combined. To implement the new concept, we leveraged the inherent heterogeneity in genetic predisposition to such complex phenotypes and emphasized a new counter intuitive phenomenon of antagonistic genetic heterogeneity, which is characterized by misalignment of the directions of genetic effects and the phenotype correlation. This analysis identified 37 loci associated with blood lipids but only one locus, FBXO33, was not reported in previous top GWAS. We, however, found strong effect of antagonistic heterogeneity that leaded to profound (quantitative and qualitative) changes in the associations with blood lipids in most, 25 of 37 or 68%, loci. These changes suggested new roles for some genes, which functions were considered as well established such as GCKR, SIK3 (APOA1 locus), LIPC, LIPG, among the others. The antagonistic heterogeneity highlighted a new class of genetic associations emphasizing beneficial and adverse trade-offs in predisposition to lipids. Our results argue that rigorous analyses dissecting heterogeneity in genetic predisposition to complex traits such as lipids beyond those implemented in current GWAS are required to facilitate translation of genetic discoveries into health care. [ABSTRACT FROM AUTHOR]

Background: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits.Methods: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity.Results: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed.Conclusions: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk. [ABSTRACT FROM AUTHOR]

Context Clinical trials examining the cardiovascular protective effects of quercetin in humans have reported conflicting results. Objective The aim of this systematic review was to summarize evidence of the effects of quercetin supplementation on plasma lipid profiles, blood pressure (BP), and glucose levels in humans by performing a meta-analysis of randomized controlled trials. Data Sources MEDLINE, Embase, and Scopus databases were searched electronically from their inception to July 2018 to identify randomized controlled trials that assessed the impact of quercetin on lipid profiles, BP, and glucose levels. Study Selection Randomized controlled trials assessing the effects of quercetin or a standardized quercetin-enriched extract on plasma lipid profiles, BP, and glucose levels in humans were eligible for inclusion. Data Extraction A random-effects model was used for data analysis. Continuous variables were expressed as weighted mean differences (WMDs) and 95%CIs. Subgroup analyses were conducted to explore possible influences of study characteristics. Sensitivity analyses were also performed, as were analyses of publication bias. Results Seventeen trials (n = 896 participants total) were included in the overall analysis. Pooled results showed that quercetin significantly lowered both systolic BP (WMD, −3.09 mmHg; 95%CI, −4.59 to −1.59; P = 0.0001) and diastolic BP (WMD, −2.86 mmHg; 95%CI, −5.09 to −0.63; P = 0.01). Neither lipid profiles nor glucose concentrations changed significantly. In subgroup analyses, significant changes in high-density lipoprotein cholesterol and triglycerides were observed in trials with a parallel design and in which participants consumed quercetin for 8 weeks or more. Conclusion Quercetin intake resulted in significantly decreased BP in humans. Moreover, participants who consumed quercetin for 8 weeks or more showed significantly changed levels of high-density lipoprotein cholesterol and triglycerides in trials with a parallel design. [ABSTRACT FROM AUTHOR]

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries.Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group.Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China.Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol. [ABSTRACT FROM AUTHOR]

Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected genetic instruments for blood levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, for cholesterol and triglycerides components of size-defined lipoprotein particles, and for lipid-modifying drug targets based on published genome-wide association studies (up to 617 303 individuals). Applying two-sample Mendelian randomization approaches we investigated associations with ischaemic and haemorrhagic manifestations of small vessel disease [small vessel stroke: 11 710 cases, 287 067 controls; white matter hyperintensities (WMH): 10 597 individuals; intracerebral haemorrhage: 1545 cases, 1481 controls]. We applied the inverse-variance weighted method and multivariable Mendelian randomization as our main analytical approaches. Genetic predisposition to higher HDL-C levels was associated with lower risk of small vessel stroke [odds ratio (OR) per standard deviation = 0.85, 95% confidence interval (CI) = 0.78-0.92] and lower WMH volume (β = -0.07, 95% CI = -0.12 to -0.02), which in multivariable Mendelian randomization remained stable after adjustments for LDL-C and triglycerides. In analyses of lipoprotein particle components by size, we found these effects to be specific for cholesterol concentration in medium-sized high-density lipoprotein, and not large or extra-large high-density lipoprotein particles. Association estimates for intracerebral haemorrhage were negatively correlated with those for small vessel stroke and WMH volume across all lipid traits and lipoprotein particle components. HDL-C raising genetic variants in the gene locus of the target of CETP inhibitors were associated with lower risk of small vessel stroke (OR: 0.82, 95% CI = 0.75-0.89) and lower WMH volume (β = -0.08, 95% CI = -0.13 to -0.02), but a higher risk of intracerebral haemorrhage (OR: 1.64, 95% CI = 1.26-2.13). Genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized high-density lipoprotein particles, is associated with both a lower risk of small vessel stroke and lower WMH volume. These analyses indicate that HDL-C raising strategies could be considered for the prevention of ischaemic small vessel disease but the net benefit of such an approach would need to be tested in a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Objective The aim was to evaluate whether T cell subsets and the lipid profile could be linked to the cardioprotective effect of IgM anti-phosphorylcholine (PC) antibodies in SLE. Methods Anti-PC antibodies were quantified by ELISA in 197 patients and 99 controls and analysed in relationship to clinical features, treatments and serum lipids. Carotid atheromatosis was evaluated by ultrasonography; Th1, Th17, Treg and CD4+CD28null cells by flow cytometry; and cytokine serum levels by immunoassays, in a subgroup of 120 SLE patients and 33 controls. Results IgM anti-PC serum levels were reduced in SLE patients compared with controls (P < 0.001) and were associated with age (β= −0.252; P = 0.002), high-density lipoprotein (HDL; β = 0.271; P = 0.001), low-density lipoprotein (LDL; β= −0.192; P = 0.017) and glucocorticoid treatment (β= −0.201; P = 0.012), whereas the IgG-to-IgM anti-PC ratio was increased (P = 0.007) and associated with age (β = 0.194; P = 0.028) and SLEDAI (β = 0.250; P = 0.005). Also, patients with clinical or subclinical cardiovascular disease exhibited reduced IgM anti-PC levels compared with their cardiovascular disease-free counterparts, regardless of glucocorticoid usage (P = 0.001). CD4+CD28null and Th17 cells were increased in SLE patients compared with controls (P < 0.01) and correlated inversely with IgM anti-PC levels. These associations were observed in patients displaying high triglyceride or low HDL levels, even after adjusting for clinical parameters and treatments (CD4+CD28null: β = −0.455, P = 0.001; Th17: β= −0.280, P = 0.035), but not in those with a normal lipid profile. High triglyceride and low HDL profiles were related to low IgM anti-PC and Treg levels, respectively, whereas both lipid profiles were associated with inflammatory markers and cytokines. Conclusion The present study provides evidence for an association of IgM anti-PC antibodies with pro-atherogenic T cell subsets in SLE, with a high triglyceride/low HDL lipid profile playing a facilitating major role. [ABSTRACT FROM AUTHOR]

Context Vitamin D deficiency is highly prevalent across the world. The existing evidence suggests vitamin D may have beneficial effects on serum lipid profiles and thus cardiovascular health. Objective The objective of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on serum lipid profiles. Data Source Original randomized controlled trials (RCTs) examining the effect of vitamin D supplementation on serum lipid profiles and published before July 2018 were identified by searching online databases, including PubMed, Google Scholar, and ScienceDirect, using a combination of relevant keywords. Data Extraction Data on study characteristics, effect size, measure of variation, type of vitamin D supplementation, and duration of follow-up were extracted by the author. Data Analysis PRISMA guidelines for systematic reviews were followed. Random effects (DerSimonian and Laird [D-V)] models were used to pool standardized mean differences in total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides between the active and the placebo arms of RCT studies. Between-study heterogeneities were assessed using Cochrane Q and I2, and publication bias was assessed using Begg's test, Egger's test, and funnel plot. Results A total of 41 RCTs comprising 3434 participants (n = 1699 in the vitamin D supplementation arm and n = 1735 in the placebo arm) were identified and included in the meta-analysis. Approximately 63.4% of study participants were women, with 14 studies conducted entirely among women. Approximately 24% of the trials had follow-up duration >6 months, whereas the remaining 76% had follow-up duration of < 6 months. The standardized mean differences (SMDs) and 95% confidence intervals (CIs) for comparing the change from baseline to follow-up between the vitamin D supplementation arm and the placebo (control) arm were as follows: total cholesterol = –0.17 (–0.28 to –0.06); LDL cholesterol = –0.12 (–0.23 to –0.01); triglycerides = –0.12 (–0.25 to 0.01); and HDL cholesterol = –0.19 (–0.44 to 0.06). After removing a trial that was an outlier based on the magnitude of the effect size, the SMD for triglycerides was –0.15 (–0.24 to –0.06) and that for HDL cholesterol was –0.10 (–0.28 to 0.09). The improvements in total cholesterol and triglycerides were more pronounced in participants with baseline vitamin D deficiency. Conclusions Vitamin D supplementation appeared to have a beneficial effect on reducing serum total cholesterol, LDL cholesterol, and triglyceride levels but not HDL cholesterol levels. Vitamin D supplementation may be useful in hypercholesterolemia patients with vitamin D insufficiency who are at high risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The intrauterine environment is critical for fetal growth and development. However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging.Methods: We used a novel two-sample Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n = 188 577 European-ancestry individuals; sample 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n = 230 069 European-ancestry individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects.Results: We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = -0.005 (95% confidence interval: -0.039, 0.029), LDL-C = 0.014 (-0.017, 0.045), and triglycerides = 0.014 (-0.025, 0.052)].Conclusions: Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes. [ABSTRACT FROM AUTHOR]

Motivation Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological 'concepts' that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression. Results We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD. We identified two subnetworks 'triacylglycerols' and 'cardiolipins-phosphatidylethanolamines (CL-PE)' characterized by lower connectivity, and a higher abundance of longer polyunsaturated triacylglycerols in patients with severe CKD (stage ≥4) from the Clinical Phenotyping Resource and Biobank Core. These finding were replicated in an independent cohort, the Chronic Renal Insufficiency Cohort. Using an innovative method for elucidating biological alterations in lipid networks, we demonstrated alterations in triacylglycerols and cardiolipins-phosphatidylethanolamines that precede the clinical outcome of end-stage kidney disease by several years. Availability and implementation A complete list of NetGSA results in HTML format can be found at http://metscape.ncibi.org/netgsa/12345-022118/cric%5fcprobe/022118/results%5fcric%5fcprobe/main.html. The DNEA is freely available at https://github.com/wiggie/DNEA. Java wrapper leveraging the cytoscape.js framework is available at http://js.cytoscape.org. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014–November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2–degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10−6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10−8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models. [ABSTRACT FROM AUTHOR]

Context Carbohydrate-restricted diets may increase low-density lipoprotein cholesterol and thereby cardiovascular risk. Objective A systematic review and meta-analyses were conducted to compare the effects of very low, low, and moderate carbohydrate, higher fat diets versus high-carbohydrate, low-fat diets on low-density lipoprotein cholesterol and other lipid markers in overweight/obese adults. Data Sources Medline, PubMed, Cochrane Central, and CINAHL Plus were searched to identify large randomized controlled trials (n > 100) with duration ≥ 6 months. Data Extraction Eight randomized controlled trials (n = 1633; 818 carbohydrate-restricted diet, 815 low-fat diet) were included. Data Analysis Quality assessment and risk of bias, a random effects model, and sensitivity and subgroup analyses based on the degree of carbohydrate restriction were performed using Cochrane Review Manager. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Results Carbohydrate-restricted diets showed no significant difference in low-density lipoprotein cholesterol after 6, 12, and 24 months. Although an overall pooled analysis statistically favored low-fat diets (0.07 mmol/L; 95% confidence interval [CI], 0.02–0.13; P = 0.009], this was clinically insignificant. High-density lipoprotein cholesterol and plasma triglycerides at 6 and 12 months favored carbohydrate-restricted diets (0.08 mmol/L; 95%CI, 0.06–0.11; P < 1 × 10−5 and −0.13 mmol/L; 95%CI, −0.19 to −0.08; P < 1 × 10−5, respectively). These favorable changes were more marked in the subgroup with very-low carbohydrate content (< 50 g/d; 0.12 mmol/L; 95%CI, 0.10–0.14; P < 1 × 10−5 and −0.19 mmol/L; 95%CI, −0.26 to −0.12; P = 0.02, respectively). Conclusions Large randomized controlled trials of at least 6 months duration with carbohydrate restriction appear superior in improving lipid markers when compared with low-fat diets. Dietary guidelines should consider carbohydrate restriction as an alternative dietary strategy for the prevention/management of dyslipidemia for populations with cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting.Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48.Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ± 38.4 mg/dL; week 48: 171.0 ± 35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ± 1.2; week 48: 4.0 ± 1.2), HDL (baseline: 49.1 ± 12.0 mg/dL; week 48: 49.2 ± 45.8 mg/dL), LDL (baseline: 119.2 ± 30.2 mg/dL; week 48: 114.2 ± 110.7 mg/dL), and triglycerides (baseline: 136.6 ± 86.8 mg/dL; week 48: 113.4 ± 67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ± 48.8 mg/dL; week 48: 173.4 ± 36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ± 1.6; week 48: 4.0 ± 1.2), HDL (baseline: 46.4 ± 12.5 mg/dL; week 48: 52.1 ± 54.4 mg/dL), LDL (baseline: 127.0 ± 36.3 mg/dL; week 48: 111.4 ± 35.8 mg/dL), and triglycerides (baseline: 167.6 ± 107.7 mg/dL; week 48: 122.7 ± 72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)].Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background. Prior research in sub-Saharan Africa reports dyslipidemia in perinatally human immunodeficiency virus (HIV)- infected children receiving ritonavir-boosted lopinavir (LPV/r) compared with efavirenz; however, interpretation of findings is limited by lack of comparison data from HIV-uninfected children. Methods. We conducted a cross-sectional analysis of lipid profiles and growth within a larger longitudinal cohort study of perinatally HIV-infected and HIV-uninfected children aged 4-9 years in Johannesburg, South Africa. At enrollment, anthropometrics, viral load, CD4, total cholesterol (TC), high-density lipoprotein, low-density lipoprotein (LDL), and triglycerides were measured. Weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), and body mass index-for-age Z-score (BAZ) were calculated. United States pediatric thresholds for dyslipidemia were used. Results. Five hundred fifty-three HIV-infected and 300 HIV-uninfected children (median age 6.9 years) of similar demographic characteristics were enrolled. Of the HIV-infected children, 94.8% were on combination antiretroviral therapy (cART) (65.4% on LPV/r- and 28.6% on efavirenz-based regimens). Among the treated, 94.3% had a viral load <200 copies/mL. Median CD4% was 34.4. The HIV-infected children had lower mean WAZ (-0.7 vs -0.3, P < .01) and HAZ (-1.1 vs -0.7, P < .01) compared with HIV-uninfected children. A lower proportion of HIV-infected children were overweight (BAZ >1) compared with HIV-uninfected children (14.4% vs 21.7%, P = .04). Whether on LPV/r or efavirenz, a higher proportion of HIV-infected children had borderline/ elevated TC or abnormal triglycerides than HIV-uninfected children, although a higher proportion of those on LPV/r had borderline/ elevated TC, borderline/elevated LDL, or abnormal triglycerides than those on efavirenz. Conclusions. In a South African cohort of HIV-infected children and population-appropriate HIV-uninfected children, unfavorable alterations in lipid profiles were detected in HIV-infected children regardless of treatment regimen compared with HIV-uninfected children. The HIV-infected children were of smaller size than HIV-uninfected children, but there was a high prevalence of overweight in both groups. Strategies for optimizing growth and early life management of lipid alterations may be warranted. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Methods: Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms; replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (ΔTC) and triglycerides (ΔTG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; Nmax = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N ∼ 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either ΔTC or ΔTG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with ΔTG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 × 10-8), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 × 10-6). The rs7412 variant at APOE was associated with ΔTC in GLACIER (P < 1.7 × 10-6). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with ΔTC and for ΔTG, respectively (P < 10-3). Of these, a variant at CAPN3 (P = 1.2 × 10-4), multiple variants at HPR (Pmin = 1.5 × 10-6) and a variant at SIX5 (P = 1.9 × 10-4) showed evidence for association with CAD.Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk. [ABSTRACT FROM AUTHOR]

The ability to transform Camelina sativa easily with biosynthetic enzymes derived from other plants has made this oil seed crop an ideal platform for the production of unusual lipids valuable for different applications. However, in addition to expressing transgenic enzymes, the suppression of endogenous enzyme activity to reduce competition for common substrates or cofactors is also required to enhance the production of target compounds. As camelina possesses a relatively undifferentiated hexaploid genome, up to three gene homeologs can code for any particular enzymatic activity, complicating efforts to alter endogenous biosynthetic pathways. New genome editing technologies, such as that offered by the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) system, offer the capability to introduce mutations into specifically targeted genomic sites. Here, by using a carefully designed guide RNA identical to all three homeologs, we demonstrate the ability of the CRISPR/Cas genome editing system to introduce mutations in all three CsDGAT1 or CsPDAT1 homeologous genes important for triacylglycerol (TAG) synthesis in developing seeds. Sequence analysis from transgenic T1 plants revealed that each CsDGAT1 or each CsPDAT1 homeolog was altered by multiple mutations, resulting in a genetic mosaic in the plants. Interestingly, seed harvested from both CsDGAT1- and CsPDAT1-targeted lines was often shrunken and wrinkled. Further, lipid analysis revealed that many lines produced seed with reduced oil content and altered fatty acid composition, consistent with the role of the targeted genes in seed oil biosynthesis. The CRISPR/Cas system therefore represents a useful method to alter endogenous biosynthetic pathways efficiently in polyploid species such as camelina. [ABSTRACT FROM AUTHOR]

Study Question: Are maternal preconception lipid levels associated with fecundability?Summary Answer: Fecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels.What Is Known Already: Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones. Evidence illustrating this relationship at the mechanistic level is mounting but few studies in humans have explored the role of preconception lipids in fecundity.Study Design, Size, Duration: A secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a block-randomized, double-blind, placebo-controlled trial.Participants/materials, Setting, Methods: A total of 1228 women, with 1-2 prior pregnancy losses and without a diagnosis of infertility, attempting pregnancy for up to six menstrual cycles were recruited from clinical sites in Utah, New York, PA and Colorado. Time to pregnancy was the number of menstrual cycles to pregnancy as determined by positive hCG test or ultrasound. Individual preconception lipoproteins were measured at baseline, prior to treatment randomization and dichotomized based on clinically accepted cut-points as total cholesterol ≥200 mg/dl, LDL-C ≥130 mg/dl, HDL-C <50 mg/dl and triglycerides ≥150 mg/dl.Main Results and the Role Of Chance: There were 148 (12.3%) women with elevated total cholesterol, 94 (7.9%) with elevated LDL-C, 280 (23.2%) with elevated triglycerides and 606 (50.7%) with low HDL-C. The fecundability odds ratio (FOR) was reduced for all abnormal lipids before and after confounder adjustment, indicating reduced fecundability. Total cholesterol ≥200 mg/dl was associated with 24% (FOR: 0.76, 95% CI: 0.59, 0.97) and 29% (FOR: 0.71, 95% CI: 0.55, 0.93) reduced fecundability for hCG-detected and ultrasound-confirmed pregnancy, respectively, compared with total cholesterol <200 mg/dl. There was a 19-36% decrease in the probability of conception per cycle for women with abnormal lipoprotein levels, though additional adjustment for central adiposity and BMI attenuated observed associations.Limitations, Reasons For Caution: Although the FOR is a measure of couple fecundability, we had only measures of female lipid levels and can therefore not confirm the findings from a previous study indicating the independent role of male lipids in fecundity. The attenuated estimates and decreased precision after adjustment for central adiposity and obesity indicate the complexity of potential causal lipid pathways, suggesting other factors related to obesity besides dyslipidemia likely contribute to reduced fecundability.Wider Implications Of the Findings: Our results are consistent with one other study relating preconception lipid concentrations to fecundity and expand these findings by adding critically important information about individual lipoproteins. As lipid levels are modifiable they may offer an inexpensive target to improve female fecundability.Study Funding and Competing Interest(s): This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have declared that no conflicts of interest exist.Trial Registration Number: #NCT00467363. [ABSTRACT FROM AUTHOR]

Study Question: What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)?Summary Answer: Insulin resistance (IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS.What Is Known Already: Obesity and IR are frequently present in both women with PCOS and subjects having NAFLD. The coexistence of PCOS and NAFLD might synergistically increase the risk for both type 2 diabetes (T2DM) and cardiovascular disease (CVD). LAP, calculated from waist circumference (WC) and triglycerides (TGs) concentrations [(WC-58) × TGs], has been shown to represent an integrated marker of cardiometabolic risk in women with PCOS.Study Design, Size, Duration: This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013.Participants, Settings, Methods: The study was done at the university hospitals in Belgrade, Serbia and Thessaloniki, Greece. All subjects underwent anthropometric measurements and analyses of fasting blood glucose, insulin, lipids, total testosterone and SHBG, as well as liver tests (transaminases, γ-glutamyltransaminase, total bilirubin and alkaline phosphatase). Calculations for a NAFLD liver fat score (NAFLD-LFS) (with, accordingly, determination of metabolic syndrome and testing for T2DM) as well as homeostasis model assessment of IR (HOMA-IR), LAP as a marker of visceral adiposity, and free androgen index (FAI) were performed. We evaluated the prevance of NAFLD and analyzed associations of the above variables with NAFLD.Main Results and the Role Of Chance: NAFLD was more prevalent in patients with PCOS than in controls (50.6 versus 34.0%, respectively). Women with PCOS had higher readings for WC, LAP, insulin and HOMA-IR, total cholesterol and TGs than controls (P < 0.001). In PCOS women, the NAFLD-LFS significantly (P < 0.001) correlated with WC, BMI, glucose, HOMA-IR, TGs, LAP and FAI. In multivariate logistic regression, HOMA-IR and LAP were independently associated with NAFLD (P ≤ 0.001).Limitations, Reasons For Caution: A possible weakness of the study may be the absence of structural confirmation of liver status. Hovewer, liver biopsy is invasive, difficult to perform in large populations and carries some risk of complications while magnetic resonance spectroscopy does not provide any information regarding the presence of fibrosis and is not routinely available. Another possible limitation could be the measurement of total testosterone by radioimmunoassay, which can be inaccurate when determining low levels of testosterone. Finally, fewer controls than subjects in the study group could have affected the significance of the results.Wider Implications Of the Findings: There is a debate on the most accurate clinical method for diagnosing liver disease as an early predictor of T2DM and CVD in general population and in PCOS women. There current study provided data on this issue from a cohort of Caucasian women with PCOS.Study Funding/competing Interests: The study was supported by a research grant by the Serbian Ministry of Science and Education (grant nos 41009 and 175032). All authors have no competing interests. [ABSTRACT FROM AUTHOR]

Prior studies observing associations between low levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease (CVD) have often been conducted among persons with metabolic or other lipid abnormalities. In this study, we investigated the association between primary low HDL cholesterol and coronary heart disease (CHD), CVD, and all-cause death after adjustment for confounders in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants who were free of clinical CVD were recruited from 6 US research centers from 2000 to 2002 and followed for a median duration of 10.2 years. We defined "primary low HDL cholesterol" as HDL cholesterol level <40 mg/dL (men) or <50 mg/dL (women), triglyceride level <100 mg/dL, and low-density lipoprotein cholesterol level <100 mg/dL (n= 158). We defined an "optimal" lipid profile as HDL cholesterol ≥40 mg/dL (men) or ≥50 mg/dL (women) and triglycerides and low-density lipoprotein cholesterol <100 mg/dL (n= 780). For participants with primary low HDL cholesterol versus those with an optimal lipid profile, adjusted hazard ratios for total CHD, CVD, and death were 2.25 (95% confidence interval (CI): 1.20,4.21; P= 0.011), 1.93 (95% CI: 1.11,3.34; P= 0.020), and 1.11 (95% CI: 0.67, 1.84; P=0.69), respectively. Participants with primary low HDL cholesterol had higher risks of CHD and CVD than participants with optimal lipid profiles but no difference in survival after a median 10.2 years of follow-up. [ABSTRACT FROM AUTHOR]

Intramuscular fat depot is of major interest for consumers, producers, and the industry. To predict intramuscular (i.m.) lipid deposition in cattle of continental breeds, different models were constructed for different muscles in bulls, steers, and cows. Two independent databases (DB1 and DB2) were developed with homogeneous individual data collected in the same slaughterhouse and total lipids, phospholipids, and triglycerides were analyzed in the same lab with the same procedures. Database DB1 was used with the meta-analysis methodology to fit the predictive models of i.m. lipids, phospholipids, and triglycerides with carcass fatness. Database DB2 was used to evaluate the accuracy of the models predicted. Total lipid and triglyceride contents varied linearly with carcass fatness in bulls, steers, and cows, but phospholipids were more independent of carcass fatness, regardless of the type of cattle studied. In bulls, LM had a lower minimal value (intercept in the model) and greater slope than semitendinosus (ST) and triceps brachii (TB) muscles. In cows, LM showed a greater intercept than ST and TB muscles but a similar slope. In steers, lipid content increased similarly in LM, rectus abdominis (RA) muscle, and ST muscle with carcass fatness. Bulls had a lower intercept than steers but showed a similar trend with carcass fatness. According to the external evaluation using DB2, the models obtained to predict total lipids in LM were more accurate than those obtained in the ST muscle in bulls and cows and in the RA muscle in steers. The models proposed for cows should be used only in the range of carcass fatness used to fit the equations, and further data are needed to fully validate them. [ABSTRACT FROM AUTHOR]

Context: Cheese may affect lipids and lipoproteins differently than other high-fat dairy foods. Objective: The present systematic review and meta-analysis was performed to evaluate randomized controlled trials that examined the effect of cheese consumption compared with another food product on blood lipids and lipoproteins. Data Sources: A systematic literature search of the MEDLINE, Embase, Scopus, CAB Abstracts, the Cochrane Controlled Trials Register, and the clinicaltrials.gov website was performed. Study Selection: A total of 12 randomized controlled trials (RCTs) were identified that examined the effect of cheese consumption on blood lipids and lipoproteins in healthy adults. Data Extraction: A meta-analysis of 5 RCTs that compared the effects of hard cheese and butter, both of which had a similar ratio of polyunsaturated fatty acids to saturated fatty acids (P/S ratio), was performed. Data Synthesis: Compared with butter intake, cheese intake (weighted mean difference: 145.0 g/d) reduced low-density lipoprotein cholesterol (LDL-C) by 6.5% (-0.22 mmol/l; 95%CI: -0.29 to -0.14) and high-density lipoprotein cholesterol (HDL-C) by 3.9% (-0.05 mmol/l; 95%CI: -0.09 to -0.02) but had no effect on triglycerides. Compared with intake of tofu or fat-modified cheese, cheese intake increased total cholesterol or LDL-C, as was expected on the basis of the P/S ratio of the diets. There was insufficient data to compare intake of cheese with intake of other foods. Conclusion: Despite the similar P/S ratios of hard cheese and butter, consumption of hard cheese lowers LDL-C and HDL-C when compared with consumption of butter. Whether these findings can be attributed to calcium, specific types of saturated fatty acids, or the food matrix of cheese warrants further research. [ABSTRACT FROM AUTHOR]

Analysis of flux of exogenously supplied [14C]fatty acid in wild-type and mutant Arabidopsis leaves indicates that DGAT1 is the predominant enzyme involved in triacylglycerol synthesis in young leaves.Triacylglycerol (TAG), typically represents <1% of leaf glycerolipids but can accumulate under stress and other conditions or if leaves are supplied with fatty acids, or in plants transformed with regulators or enzymes of lipid metabolism. To better understand the metabolism of TAG in leaves, pulse–chase radiolabelling experiments were designed to probe its synthesis and turnover. When Arabidopsis leaves were incubated with [14C]lauric acid (12:0), a major initial product was [14C]TAG. Thus, despite low steady-state levels, leaves possess substantial TAG biosynthetic capacity. The contributions of diacylglycerol acyltransferase1 and phospholipid:diacylglycerol acyltransferase1 to leaf TAG synthesis were examined by labelling of dgat1 and pdat1 mutants. The dgat1 mutant displayed a major (76%) reduction in [14C]TAG accumulation whereas pdat1 TAG labelling was only slightly reduced. Thus, DGAT1 has a principal role in TAG biosynthesis in young leaves. During a 4h chase period, radioactivity in TAG declined 70%, whereas the turnover of [14C]acyl chains of phosphatidylcholine (PC) and other polar lipids was much lower. Sixty percent of [14C]12:0 was directly incorporated into glycerolipids without modification, whereas 40% was elongated and desaturated to 16:0 and 18:1 by plastids. The unmodified [14C]12:0 and the plastid products of [14C]12:0 metabolism entered different pathways. Although plastid-modified 14C-labelled products accumulated in monogalactosyldiacylglycerol, PC, phosphatidylethanolamine, and diacylglcerol (DAG), there was almost no accumulation of [14C]16:0 and [14C]18:1 in TAG. Because DAG and acyl-CoA are direct precursors of TAG, the differential labelling of polar glycerolipids and TAG by [14C]12:0 and its plastid-modified products provides evidence for multiple subcellular pools of both acyl-CoA and DAG. [ABSTRACT FROM PUBLISHER]

Background: Tobacco smoking has been associated with cardiovascular risk factors including adverse serum lipid levels, central obesity and higher resting heart rate, but lower blood pressure and body mass index (BMI). We used a Mendelian randomization approach to study whether these associations may be causal. If smoking affects cardiovascular risk factors then rs1051730 T alleles, predictors of increased smoking quantity, should be associated with cardiovascular risk factors among smokers, but not among never smokers.Methods: Among 56,625 participants of a population-based study, we estimated associations of rs1051730 T alleles with cardiovascular risk factors and examined whether the associations differed by smoking status.Results: Rs1051730 T alleles were associated with lower BMI and waist and hip circumferences and higher resting heart rate and estimated glomerular filtration rate (eGFR), and the associations were strongest among current smokers (P interaction 5×10(-9) to 0.01). Rs1051730 T alleles were associated with lower systolic blood pressure and pulse pressure and higher HDL cholesterol concentrations, but these associations did not robustly differ by smoking status. There were no convincing associations of rs1051730 T alleles with waist-hip ratio, diastolic blood pressure and non-fasting serum concentrations of non-HDL cholesterol, triglycerides, glucose and C-reactive protein.Conclusions: This Mendelian randomization analysis provides evidence that smoking may cause lower BMI and waist and hip circumferences and higher resting heart rate and eGFR. The findings further suggest that smoking is not a major determinant of waist-hip ratio or adverse blood pressure, serum lipid or glucose levels. [ABSTRACT FROM AUTHOR]

To evaluate the effect of feeding thermally oxidized vegetable oils and animal fats on growth performance, liver gene expression, and liver and serum fatty acid and cholesterol concentration in young pigs, 102 barrows (6.67 ± 0.03 kg BW) were divided into 3 groups and randomly assigned to dietary treatments in a 4 x 3 factorial arrangement. The main factors were lipid source (n = 4; corn oil [CN], canola oil [CA], poultry fat [PF], and tallow [TL]) and lipid peroxidation level (n = 3; original lipids [OL], slow oxidation [SO] through heating at 95°C for 72 h, or rapid oxidation [RO] through heating at 185°C for 7 h). Pigs were provided ad libitum access to diets in group pens for 28 d followed by controlled feed intake in metabolism crates for 10 d. On d 39, all pigs were euthanized for liver samples to determine liver weight, lipid profile, and gene expression patterns. Lipid oxidation analysis indicated that compared with the OL, SO and RO of lipids had a markedly increased concentrations of primary and secondary peroxidation products, and the increased lipid peroxidation products in CN and CA were greater than those in PF and TL. After a 28-d ad libitum feeding period, pigs fed RO lipids tended to have reduced ADFI (P = 0.09) and ADG (P < 0.05) compared with pigs fed OL, and pigs fed CA had reduced G:F (P < 0.05) compared with pigs fed all other lipids. Pigs fed RO lipids tended to have increased relative liver weight (P = 0.09) compared with pigs fed OL. Liver triglyceride concentration (LTG) in pigs fed OL was greater (P < 0.05) than in pigs fed SO lipids and tended to be greater (P < 0.07) than in pigs fed SO. The reduced LTG were consistent with increased (P < 0.05) mRNA expression of PPARa factor target genes (acyl-CoA oxidase, carnitine palmitoyltransferase 1, and mitochondrial 3-hydroxy-3-methylglutary-CoA synthase) in pigs fed SO and RO lipids compared with pigs fed OL. Pigs fed CN or CA tended to have increased LTG {P = 0.09) compared with pigs fed TL. Liver cholesterol concentration in pigs fed CN was less (P < 0.05) than in pigs fed PF and tended to be less (P = 0.06) than in pigs fed TL, whereas pigs fed CA had a reduced (P < 0.05) liver cholesterol compared with pigs fed PF or TL. In conclusion, feeding thermally oxidized lipids negatively affected growth performance and LTG of young pigs, which was associated with an upregulation of fatty acid catabolism pathways. [ABSTRACT FROM AUTHOR]

Objective: Although C-reactive protein (CRP) is among the best cardiovascular disease risk predictors, data regarding the association of CRP and menopause are controversial. In this study, we measured CRP by a high-sensitivity method (hsCRP), cholesterol, lipoproteins, and triglycerides in normal and overweight postmenopausal women. Methods: Body weight, height, waist circumference (WC), hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, and lipoprotein (a) were measured in 30 normal weight and 60 overweight healthy postmenopausal women. Results: Significantly higher triglyceride and hsCRP levels (P =0.005 and P <0.001 respectively), together with lower HDL-c levels (P =0.001) were found in overweight compared to normal weight women. In the overweight group, positive correlations of hsCRP were observed with age, body mass index and WC (P =0.016, P=0.001, and P <0.001, respectively) and a negative correlation was observed with HDL-c (P =0.007). In the normal weight group, positive correlations were found for hsCRP with age and WC (P =0.023 and P =0.014, respectively). WC was the best predictor of hsCRP level in both groups (P <0.001). Conclusion: Elevated hsCRP levels in conjunction with abnormal lipid profiles may be strongly associated with weight gain in postmenopausal women. Efforts to reduce obesity and inflammation in this group may help correct abnormal levels of hsCRP and lipids. [ABSTRACT FROM AUTHOR]

Background: Blood lipids levels dysregulation represent potential mechanism intermediating the adverse cardiovascular effects of ambient particulate matter (PM) exposure. The present study aims to estimate the effect of particulate matter (PM10) exposure on blood lipid levels (TC, Total Cholesterol; HDL-C, High-Density Lipoprotein Cholesterol; LDL-C, Low-Density Lipoprotein Cholesterol; TG, Triglycerides) in the adult Portuguese mainland population and to assess the potential mediation and/or modification action of abdominal obesity on this effect. Methods: We used data from 2390 participants of the 1st Portuguese Health Examination Survey (INSEF, 2015) with available data on blood lipids parameters and living within a 30km radius of an air quality monitoring station with available PM10 measurements. PM10 concentrations were acquired from the air quality monitoring network of the Portuguese Environment Agency. Generalized linear models were used to assess the effect of 1-year PM10 exposure on blood lipids values. An interaction term was introduced in the models to test the modification action of abdominal obesity. Results: We found an association between long-term exposure to PM10 and non-fasting blood TG levels after adjustment for age, sex, education, occupation, lifestyles related variables and temperature but only in participants with abdominal obesity (1.84% TG increase per each 1 μg/m3 PM10 increment, 95% CI: 0.02%; 3.69%) which is well supported by the sensitivity analysis. Conclusions: Our study demonstrate that even at low levels of exposure, long-term PM10 exposure interacts with abdominal obesity to increase blood TG levels. To the best of our knowledge, this is the first study showing the modification action of abdominal obesity regarding the PM10 effect on a blood lipid parameter. Our findings suggest that reducing both abdominal obesity prevalence and PM10 below current standards would result in additional health benefits for the population. Key messages: Long-term PM10 exposure interacts with abdominal obesity to increase non-fasting blood triglycerides levels by about 2% per each 1 μg/m3 PM10 increase. Reducing both abdominal obesity prevalence and PM10 below current standards would result in additional health benefits for the population. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia is associated with an increased risk of heart disease. The effect of garlic on blood lipids has been studied in numerous trials and summarized in meta-analyses, with conflicting results. This meta-analysis, the most comprehensive to date, includes 39 primary trials of the effect of garlic preparations on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. The findings suggest garlic to be effective in reducing total serum cholesterol by 17 ± 6 mg/dL and low-density lipoprotein cholesterol by 9 ± 6 mg/dL in individuals with elevated total cholesterol levels (>200 mg/dL), provided garlic is used for longer than 2 months. An 8% reduction in total serum cholesterol is of clinical relevance and is associated with a 38% reduction in risk of coronary events at 50 years of age. High-density lipoprotein cholesterol levels improved only slightly, and triglycerides were not influenced significantly. Garlic preparations were highly tolerable in all trials and were associated with minimal side effects. They might be considered as an alternative option with a higher safety profile than conventional cholesterol-lowering medications in patients with slightly elevated cholesterol. [ABSTRACT FROM AUTHOR]

The performance of a genome scan for serum lipid traits at 45 and 190 d in 5 half-sib families of Duroc pigs allowed us to detect several pig chromosomal regions with significant effects on these phenotypes. In the current work, we aimed to refine the position of 1 chromosome 4 (SSC4) genome-wide significant QTL for serum triglyceride concentration at 190 d. Genotyping of 4 additional microsatellites allowed reduction of the 90% confidence interval of this QTL to the genomic interval between markers SW2409 and SW839. Sequencing experiments were performed to characterize the variability of 2 lipid-related genes, the lipoprotein receptor-related protein 12 (LRP12) and tribbles homolog 1 (TRIB1) loci, that map to this region. In this way, 2 (c.771A > G and C.1101A > G) and 1 (C.* 156 157del) polymorphisms were identified at the LRP12 coding region and TRIB13' untranslated region, respectively. Association analyses between LRP12 and TRIB1 genotypes did not reveal any significant effect on serum lipid concentrations, suggesting that variation of these two loci does not explain the segregation of the SSC4 QTL. However, highly significant associations were observed for gluteus medius saturated fatty acid content (LRP12 C.1101A > G, P = 0.0006; TRIBl c.*156 157del, P = 0.0003). In the light of these and other findings, the potential involvement of LRP12 and TRIBl in muscle lipid metabolism deserves to be further explored. [ABSTRACT FROM AUTHOR]

Objective: to explore the relationship between blood lipids/lipoproteins and cognitive function in the Chinese oldest-old.Design: multivariate statistical analysis using cross-sectional data.Setting: community-based setting in longevity areas in China.Subjects: eight hundred and thirty-six subjects aged 80 and older were included in the sample.Methods: plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure and fasting plasma glucose were measured and information about demographics and lifestyle was collected. Cognitive status was assessed using the Mini-Mental State Examination (MMSE).Results: cumulative logit model analysis showed that triglyceride was significantly negatively associated with cognitive impairment. By general linear modelling, there was a significant linear trend of MMSE scores with the level of triglyceride, but not with levels of cholesterol after adjustment. The odds ratio (OR) of cognitive impairment (MMSE score < 18) was significantly reduced for the highest quartile of plasma triglyceride concentration (OR: 0.52, 95% CI: 0.33–0.84), but not for the second or third quartile, compared with the lowest quartile (adjusted models). There were no significant associations between cognitive impairment and cholesterol.Conclusion: we concluded that high normal plasma triglyceride was associated with preservation of cognitive function while lower concentrations were not in the Chinese oldest-old. [ABSTRACT FROM PUBLISHER]