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Background: Lipid levels have been suggset to be correlated with multiple myeloma (MM) risk, though causality remains unconfirmed. To explore this further, a detailed study combining meta-analysis and Mendelian randomization (MR) was conducted. Methods: Literature searches were performed on PubMed and Embase; summary data for plasma lipid traits were extracted from the IEU and MM data from the FinnGen database. Meta-analysis and MR were utilized to analyze the link of lipids with MM risk, including mediator MR to identify potential mediators. The study was conducted in accordance with PRISMA and STROBE-MR guidelines. Results: Observational studies analyzed through meta-analysis showed that elevated levels of LDL, HDL, total cholesterol (TC), and triglycerides correlate with a lower risk of MM, with HRs of 0.73, 0.59, 0.60, and 0.84, respectively. MR analysis confirmed a potential causal link of triglyceride with a reduced MM risk (OR: 0.67, 95% CI: 0.46–0.98), independent of BMI. Mediation analysis pointed to X-11,423-O-sulfo-L-tyrosine and neuropilin-2 as potential mediators. Conclusions: The findings suggest that higher lipid levels (LDL, HDL, TC, and triglycerides) are linked with a reduced MM risk, and higher triglyceride levels are causally associated with a reduced MM risk. This suggests new avenues for therapeutic interventions targeting MM. [ABSTRACT FROM AUTHOR]

Background and objective: Hemorrhagic stroke, characterized by acute bleeding due to cerebrovascular lesions, is associated with plasma lipids and endothelial damage. The causal relationship between genetic plasma lipid levels and hemorrhagic stroke remains unclear. This study employs a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between plasma lipid profiles with different fatty acid chains and the risk of intracerebral and subarachnoid hemorrhage, the two main subtypes of hemorrhagic stroke. Methods: The datasets for exposure and outcome summary statistics were obtained from publicly available sources such as the GWAS Catalog, IEU OpenGWAS project, and FinnGen. The two-sample MR analysis was employed to initially assess the causal relationship between 179 plasma lipid species and the risk of intracerebral and subarachnoid hemorrhage in the Finnish population, leading to the identification of candidate lipids. The same methods were applied to reanalyze data from European populations and conduct a meta-analysis of the candidate lipids. The Inverse Variance Weighting (IVW) method served as the primary analysis for causal inference, with additional methods used for complementary analyses. Sensitivity analysis was conducted to clarify causal relationships and reduce biases. Results: Two analyses using Mendelian randomization were performed, followed by meta-analyses of the results. A causal relationship was established between 11 specific lipid species and the occurrence of intracerebral hemorrhage within the European population. Additionally, 5 distinct lipid species were associated with subarachnoid hemorrhage. Predominantly, lipids with linoleic acid and arachidonic acid side chains were identified. Notably, lipids containing arachidonic acid chains (C20:4) such as PC 18:1;0_20:4;0 consistently showed a decreased risk of both intracerebral hemorrhage [p < 0.001; OR(95% CI) = 0.892(0.835-0.954)] and subarachnoid hemorrhage [p = 0.002; OR(95% CI) = 0.794(0.689-0.916)]. Conversely, lipids with linoleic acid chains (C18:2) were associated with an increased risk of intracerebral hemorrhage. Conclusion: This study identifies a potential causal relationship between lipids with different fatty acid side chains and the risk of intracerebral and subarachnoid hemorrhagic stroke, improving the understanding of the mechanisms behind the onset and progression of hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables. Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied. No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1. These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition. [ABSTRACT FROM AUTHOR]

Abstract Background Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway. Methods We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran’s Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings. Results The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929–0.972, p = 6.65 × 10− 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906–0.971, p = 2.79 × 10− 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906–0.969, p = 1.48 × 10− 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876–0.961, p = 2.72 × 10− 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028–1.079, p = 2.11 × 10− 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039–1.135, p = 2.47 × 10− 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%. Conclusion Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is a multifactorial, multisystemic syndrome that involves alterations in lipid metabolism. This study aimed to test whether distinct plasma lipid profiles or lipid entities or both are associated with clinical and functional echocardiographic parameters in HFpEF. Methods and results We examined the human plasma lipidome in HFpEF patients (n = 18) with left ventricular ejection fraction ≥50% and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) >125 pg/mL and control subjects (n = 12) using mass spectrometry‐based shotgun lipidomics. The cohort included 8 women and 22 men with average age of 67.8 ± 8.6 SD. The control and disease groups were not significantly different with respect to age, body mass index, systolic and diastolic blood pressure, and waist‐to‐hip ratio. The disease group experienced more fatigue (P

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle‐aged and elderly population, particularly CKD patients. We conducted a cross‐sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high‐density lipoprotein cholesterol (HDL‐C) levels increased with age. In the CKD and non‐CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non‐CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = −0.002, p < 0.001). HDL‐C showed a positive correlation with eGFR (r = 0.001, p < 0.001). [Correction added on 1 July 2024, after first online publication: The value of r in the preceding sentence has been updated to r = 0.001.] That is, in the middle‐aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL‐C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway. Methods: We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran's Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings. Results: The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929–0.972, p = 6.65 × 10− 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906–0.971, p = 2.79 × 10− 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906–0.969, p = 1.48 × 10− 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876–0.961, p = 2.72 × 10− 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028–1.079, p = 2.11 × 10− 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039–1.135, p = 2.47 × 10− 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%. Conclusion: Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial, multisystemic syndrome that involves alterations in lipid metabolism. This study aimed to test whether distinct plasma lipid profiles or lipid entities or both are associated with clinical and functional echocardiographic parameters in HFpEF. Methods and results: We examined the human plasma lipidome in HFpEF patients (n = 18) with left ventricular ejection fraction ≥50% and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) >125 pg/mL and control subjects (n = 12) using mass spectrometry‐based shotgun lipidomics. The cohort included 8 women and 22 men with average age of 67.8 ± 8.6 SD. The control and disease groups were not significantly different with respect to age, body mass index, systolic and diastolic blood pressure, and waist‐to‐hip ratio. The disease group experienced more fatigue (P < 0.001), had more often coronary artery disease (P = 0.04), and received more medications (beta‐blockers, P < 0.001). The disease group had significantly different levels of HFpEF‐relevant parameters, including NT‐proBNP (P < 0.001), left ventricular mass index (P = 0.005), left atrial volume index (P = 0.001), and left ventricular filling index (P < 0.001), and lower left ventricular end‐diastolic diameter (P = 0.014), with no difference in left ventricular ejection fraction. Significant differences in lipid profiles between HFpEF patients and controls could not be detected, including no significant differences in abundance of circulating lipids binned by carbon chain length or by double bonds, nor at the level of individual lipid species. However, there was a striking correlation between selected lipids with smoking status that was independent of disease status, as well as between specific lipids and hyperlipidaemia [with corresponding significance of either false discovery rate (FDR) <0.1 or FDR < 0.01]. In an exploratory network analysis of correlations, we observed significantly stronger correlations within the HFpEF group between individual lipids from the cholesterol ester and phosphatidylcholine (PC) classes and clinical/echocardiographic parameters such as left atrial volume index, left ventricular end‐diastolic diameters, and heart rate (FDR < 0.1). In contrast, the control group showed significantly stronger negative correlations (FDR < 0.1) between individual species from the PC and sphingomyelin classes and left ventricular mass index or systolic blood pressure. Conclusions: We did not find significant direct associations between plasma lipidomic parameters and HFpEF and therefore could not conclude that any specific lipids are biomarkers of HFpEF. The validation in larger cohort is needed to confidently conclude the absence of first‐order associations. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that lipid-related indicators are associated with testosterone deficiency. However, it is difficult to determine which indicator is the most accurate predictor of testosterone deficiency. We aimed to identify the lipid-related indicators most predictive of testosterone deficiency in adults in the United States. Methods: This observational research was conducted on a population aged ≥ 20 years. By plotting the receiver operating characteristic curve (ROC) and obtaining the corresponding area under the curve (AUC) value, we assessed the predictive capacity of TyG, WTI, LAP, and VAI for testosterone deficiency. We compared the area under the curve (AUC) values of these measures to determine if there were any statistically significant differences. The relationship between lipid-related indices and testosterone hormones was investigated using regression modeling, eXtreme Gradient Boosting (XGBoost) modeling, and sensitivity analysis. Results: A total of 3,272 eligible participants were included in the study. Testosterone deficiency was found to exist in 20.63% of the participants. Subjects with higher lipid-related markers were more likely to have lower testosterone levels. LAP was the best predictor of testosterone deficiency in ROC analysis over other indicators (AUC = 0.7176, (95% CI: 0.6964–0.7389)). Conclusion: LAP is the most straightforward and convenient indicator for identifying testosterone deficiency in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating data on the associations between food consumption and lipid composition in the body is essential for understanding the effects of dietary habits on health. Objectives: As part of omics research in the Tohoku Medical Megabank Community-Based Cohort Study, this study sought to reveal the dietary impact on plasma lipid concentration in a Japanese population. Methods: We conducted a correlation analysis of food consumption and plasma lipid concentrations measured using mass spectrometry, for 4032 participants in Miyagi Prefecture, Japan. Results: Our analysis revealed 83 marked correlations between six food categories and the concentrations of plasma lipids in nine subclasses. Previously reported associations, including those between seafood consumption and omega-3 fatty acids, were validated, while those between dairy product consumption and odd-carbon-number fatty acids (odd-FAs) were validated for the first time in an Asian population. Further analysis suggested that dairy product consumption is associated with odd-FAs via sphingomyelin (SM), which suggests that SM is a carrier of odd-FAs. These results are important for understanding odd-FA metabolism with regards to dairy product consumption. Conclusion: This study provides insight into the dietary impact on plasma lipid concentration in a Japanese population. [ABSTRACT FROM AUTHOR]

The Nutritional and therapeutic benefits of lycopene from red tomatoes and its products cannot be overemphasized. Therefore, this study aimed to evaluate the hypolipidaemic effect of lycopene in three different preparations of red tomatoes in hyperlipidemic rats. Forty male Wistar rats were used for the study. The rats were divided into four groups (A - D) of 10 animals each. Group A was used as the control and received basal home diet throughout the duration of the experiment. Groups B, C, and D were fed with hyperlipidemic diets for one month, followed by lycopene in three different preparations of red tomatoes (Raw tomatoes, Tomato juice, and Cooked tomatoes) for another one month. Body weight and growth rate of the rats were monitored. The serum lipid profiles of the rats after administration of the hyperlipidaemic diet as well as after treatment with red tomato preparations were determined following standard procedures. Results showed that lycopene reduced weight gain induced by hyperlipidaemic diet, increased faecal fat content, and significantly reduced hyperlipidaemia in rats. The cooked tomatoes had the greatest effect in lowering serum total cholesterol, low density lipoprotein, and increasing high density lipoprotein levels. This suggests that lycopene present in cooked tomatoes are more readily absorbed in the intestine and therefore achieve higher concentration in the blood. Based on the findings from this study, dietary red tomatoes rich in lycopene may play a significant role in weight reduction, and in lowering plasma cholesterol which directly or indirectly reduces the risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Kiwifruit contain many components, some considered beneficial, such as vitamins, phytochemicals and dietary fibre, and others potentially harmful, such as fructose and glucose in fruit sugars. In a 6-week, randomised, crossover study aimed at exploring the net effects of daily consumption of kiwifruit, 23 healthy participants consumed two Actinidia chinensis var. chinensis 'Zesy002' (marketed as Zespri™ SunGold™ Kiwifruit) per day as part of their customary diet (intervention) or without kiwifruit (control) as their customary diet for 6 weeks in a cross-over study. Anthropometric data, venous blood, and urine samples were collected at the start and end of the 6-week intervention and control periods for the measurement of physical changes, plasma glucose, insulin, glycated haemoglobin, short-chain fatty acids, blood lipids, uric acid, inflammatory biomarkers, and urinary ascorbic acid. Variables were measured between the start and finish of interventions, and between intervention and control periods. Food diaries were completed on the 3 days before blood sampling to estimate dietary ascorbic acid and dietary fibre intakes. Despite urinary vitamin C and food diaries indicating compliance, and good precision in measurements, there were no appreciable changes in biomarkers during the study, either within or between intervention and control periods, that would indicate a change in health status. Thus, the sizes of any effects of kiwifruit ingestion were too small to become significant under the test conditions used, indicating a high probability that daily ingestion of two SunGold kiwifruit is safe with respect to metabolic health. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence, pattern, and associated factors of dyslipidemia in patients with coronary artery disease (CAD) in the Northwest region of Pakistan. Method: A cross-sectional secondary data analysis was performed on CAD patients visiting cardiology clinics in selected hospitals from July to December 2019. A total of 362 patients were included via consecutive sampling. Dyslipidemia was operationalized according to the “National Cholesterol Education Program (NCEP ATP III) guidelines”. Results: Mixed dyslipidemia was recorded in 92.26% of the patients, while isolated dyslipidemia was observed in 5.24%. A high prevalence of combined dyslipidemia with increased LDL-C, TG, and low HDL-C was noted. Contrarily, elevated LDL-C was the commonest single lipid disorder (84.25%). Hypercholesterolemia was the least common disorder. Increasing BMI was found to be independently associated with hypercholesterolemia (OR: 1.19). Similarly, age (OR: 0.97) and being a rural resident (OR: 2.61) were independent factors associated with hypertriglyceridemia. Furthermore, being an urban resident (OR: 2.25) and increasing BMI (OR: 1.77) were also significantly associated with high LDL-C. Conclusion: Mixed dyslipidemias were observed in the majority of the patients. Age, BMI, and residence were noted to be independently associated with abnormal lipids. Early screening and proper management should be encouraged to minimize this significant cardiovascular risk. [ABSTRACT FROM AUTHOR]

The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology. [ABSTRACT FROM AUTHOR]

Patients with non-alcoholic steatohepatitis (NASH) show significantly faster progress in the stages of fibrosis compared to those with non-alcoholic fatty liver (NAFL) disease. The non-invasive diagnosis of NASH remains an unmet clinical need. Preliminary data have shown that sphingolipids, especially ceramides, fatty acids, and other lipid classes may be related to the presence of NASH and the histological activity of the disease. The aim of our study was to assess the association of certain plasma lipid classes, such as fatty acids, acylcarnitines, and ceramides, with the histopathological findings in patients with NASH. The study included three groups: patients with NASH (N = 12), NAFL (N = 10), and healthy [non non-alcoholic fatty liver disease (NAFLD)] controls (N = 15). Plasma samples were collected after 12 h of fasting, and targeted analyses for fatty acids, acylcarnitines, and ceramides were performed. Baseline clinical and demographic characteristics were collected. There was no significant difference in baseline characteristics across the three groups or between NAFL and NASH patients. Patients with NASH had increased levels of several fatty acids, including, among others, fatty acid (FA) 14:0, FA 15:0, FA 18:0, FA 18:3n3, as well as Cer(d18:1/16:0), compared to NAFL patients and healthy controls. No significant difference was found between NAFL patients and healthy controls. In conclusion, patients with NASH exhibited a distinctive plasma lipid profile that can differentiate them from NAFL patients and non-NAFLD populations. More data from larger cohorts are needed to validate these findings and examine possible implications for diagnostic and management strategies of the disease. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of dietary supplementation with modified-hen-egg-yolk on plasma lipids and lipoprotein profiles in rats. During the four-week-experiment, 64 Wistar rats were divided into four groups of 16 (eight of both sexes), and fed commercial rat food (group C); food containing 70% commercial rat mixture and 30% freshly cooked egg yolk originating from laying hen eggs fed with 3% fish oil (group F); 3% palm olein (group P), or 3% lard (group L). The cooked egg yolk in the rat diet affected the concentrations of plasma total and LDL-cholesterol in males of the P and L groups. Cholesterol and total fat in the diet did not have a hypercholesterolemic effect on their own, but when in combination with fatty acid composition, they could contribute to an increase in plasma total and LDL cholesterol concentrations in rats. HDL-cholesterol was the most resilient plasma lipoprotein of rats to dietary treatments in our experiment. Compared to the control group, the addition of hen egg yolk to the rat diet regardless of its quality, adversely affected the values of HDL-C/TC and HDL-C/LDL-C in both males and females.

Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are rarely comparable, which increases the need for the implementation of internationally agreed upon protocols. We performed an interlaboratory comparison for the MS-based quantitative analysis of total oxylipins. Five independent laboratories assessed the technical variability and comparability of 133 oxylipins using a harmonized and standardized protocol, common biological materials (i.e., seven quality control plasmas), standard calibration series, and analytical methods. The quantitative analysis was based on a standard calibration series with isotopically labeled internal standards. Using the standardized protocol, the technical variance was within ±15% for 73% of oxylipins; however, most epoxy fatty acids were identified as critical analytes due to high variabilities in concentrations. The comparability of concentrations determined by the laboratories was examined using consensus value estimates and unsupervised/supervised multivariate analysis (i.e., principal component analysis and partial least squares discriminant analysis). Interlaboratory variability was limited and did not interfere with our ability to distinguish the different plasmas. Moreover, all laboratories were able to identify similar differences between plasmas. In summary, we show that by using a standardized protocol for sample preparation, low technical variability can be achieved. Harmonization of all oxylipin extraction and analysis steps led to reliable, reproducible, and comparable oxylipin concentrations in independent laboratories, allowing the generation of biologically meaningful oxylipin patterns.

Summary: Background: Genetic inactivation and pharmacologic inhibition of the microsomal triglyceride transfer protein (MTP; gene name MTTP) inhibits hepatic secretion of VLDL, thereby reducing serum lipids and apoB at the expense of increasing hepatic steatosis. Aim: To examine the effects of missense variants in MTTP on hepatic and circulating lipids. Methods: We analysed the association of MTTP missense variants with metabolic, hepatic and clinical phenotypes in the Penn Medicine Biobank (PMBB; n = 37,960) and the UKBiobank (UKB; n = 451,444). Results: We analysed 24 missense variants in MTTP in PMBB for association with biopsy‐proven hepatic steatosis and found that an isoleucine 128 to threonine variant (I128T: rs3816873‐A, frequency 26%) was associated with reduced steatosis (p < 0.001). PMBB subjects with imaging‐proven steatosis also revealed significantly fewer carriers of MTTP I128T compared to controls. Analysis in UKB also showed that MTTP I128T was associated with reduced risk of hepatic steatosis. Unexpectedly, MTTP I128T was found to be associated with reduced plasma levels of LDL‐cholesterol and apoB (all p < 0.001). Functional studies indicated that MTTP I128T is neither a classic loss nor gain of function allele. Conclusions: MTTP I128T is associated with reduced hepatic steatosis as well as reduced plasma lipids and apoB. This paradoxical profile is not consistent with a simple gain or loss of function in MTP activity and suggests a more complex effect on MTP function. Further investigation of MTTP I128T will provide insight into the structure–function of MTP and potentially new approaches to modulate MTP activity that could both reduce hepatic and circulating lipids. [ABSTRACT FROM AUTHOR]

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed, Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius's health-promoting properties. [ABSTRACT FROM AUTHOR]

We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and p-values were calculated through adaptive permutation tests by the PLINK software, v1.9. Over one-year rosuvastatin therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm < 0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm < 0.05). In conclusion, polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients. [ABSTRACT FROM AUTHOR]

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice. However, the physiological role of continuous infusion of recombinant APOA4 protein in regulating sympathetic activity, thermogenesis, and lipid and glucose metabolism in low-fat-diet (LFD)-fed mice remained elusive. The hypothesis of this study was that continuous infusion of mouse APOA4 protein would increase sympathetic activity and thermogenesis in BAT and subcutaneous inguinal white adipose tissue (IWAT), attenuate plasma lipid levels, and improve glucose tolerance. To test this hypothesis, sympathetic activity, BAT temperature, energy expenditure, body weight, fat mass, caloric intake, glucose tolerance, and levels of BAT and IWAT thermogenic and lipolytic proteins, plasma lipids, and markers of fatty acid oxidation in the liver in mice with APOA4 or saline treatment were measured. Plasma APOA4 levels were elevated, BAT temperature and thermogenesis were upregulated, and plasma triglyceride (TG) levels were reduced, while body weight, fat mass, caloric intake, energy expenditure, and plasma cholesterol and leptin levels were comparable between APOA4- and saline-treated mice. Additionally, APOA4 infusion stimulated sympathetic activity in BAT and liver but not in IWAT. APOA4-treated mice had greater fatty acid oxidation but less TG content in the liver than saline-treated mice had. Plasma insulin in APOA4-treated mice was lower than that in saline-treated mice after a glucose challenge. In conclusion, continuous infusion of mouse APOA4 protein stimulated sympathetic activity in BAT and the liver, elevated BAT thermogenesis and hepatic fatty acid oxidation, and consequently attenuated levels of plasma and hepatic TG and plasma insulin without altering caloric intake, body weight gain and fat mass. [ABSTRACT FROM AUTHOR]

Although a growing number of studies have attempted to uncover the relationship between plasma lipids and the risk of aortic aneurysm (AA), it remains controversial. Meanwhile, the relationship between plasma lipids and the risk of aortic dissection (AD) has not been reported on. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the potential relationship between genetically predicted plasma levels of lipids and the risk of AA and AD. Summary data on the relationship between genetic variants and plasma lipids were obtained from the UK Biobank and Global Lipids Genetics Consortium studies, and data on the association between genetic variants and AA or AD were taken from the FinnGen consortium study. Inverse-variance weighted (IVW) and four other MR analysis methods were used to evaluate effect estimates. Results showed that genetically predicted plasma levels of low-density lipoprotein cholesterol, total cholesterol, or triglycerides were positively correlated with the risk of AA, and plasma levels of high-density lipoprotein cholesterol were negatively correlated with the risk of AA. However, no causal relationship was found between elevated lipid levels and the risk of AD. Our study revealed a causal relationship between plasma lipids and the risk of AA, while plasma lipids had no effect on the risk of AD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of dietary supplementation with modified-hen-egg-yolk on plasma lipids and lipoprotein profiles in rats. During the four-week-experiment, 64 Wistar rats were divided into four groups of 16 (eight of both sexes), and fed commercial rat food (group C); food containing 70% commercial rat mixture and 30% freshly cooked egg yolk originating from laying hen eggs fed with 3% fish oil (group F); 3% palm olein (group P), or 3% lard (group L). The cooked egg yolk in the rat diet affected the concentrations of plasma total and LDL-cholesterol in males of the P and L groups. Cholesterol and total fat in the diet did not have a hypercholesterolemic effect on their own, but when in combination with fatty acid composition, they could contribute to an increase in plasma total and LDL cholesterol concentrations in rats. HDL-cholesterol was the most resilient plasma lipoprotein of rats to dietary treatments in our experiment. Compared to the control group, the addition of hen egg yolk to the rat diet regardless of its quality, adversely affected the values of HDL-C/TC and HDL-C/LDL-C in both males and females. [ABSTRACT FROM AUTHOR]

Sargassum binderi is a brown algae abundantly available, good nutrient, cheap, does not compete with human, and has not been used optimally as feed for laying hens. Therefore, the purpose of this study was to study the effect of using fermented S. binderi on plasma lipid profiles, fat content, and cholesterol in yolk in laying hens. This study used 200 laying hens (1571-1586 g), aged from 60 to 68 weeks randomized into five different concentrations (0%, 4%, 8%, 12%, and 16%) with a length of 6 weeks. At the end of the study, blood samples were randomly taken from 40 laying hens (2 laying hens per treatment) and 80 eggs were collected randomly (4 eggs per treatment). Variables measured were plasma lipid profile (triglycerides, total cholesterol, and LDL), lipid, and yolk cholesterol. The results showed that the treatment of S. binderi had a significant effect on the lipid profile of laying hens blood serum for total cholesterol and LDL but had no significant impact on blood serum triglycerides. In addition, there was no significant effect on yolk fat and significantly on yolk cholesterol. Thus, the provision of S. binderi to 16% in the laying hen's diet can reduce total blood serum cholesterol from 211.60 to 152.49 mg/dl and LDL from 95.55 to 49.05 mg/dl, with a decrease of 27.93%, and 48.66%, respectively, and decreased yolk cholesterol from 1,279.54 to 1,074.30 mg/100 g with a reduction of 16.04%. [ABSTRACT FROM AUTHOR]

Dietary lipids induce apolipoprotein A4 (APOA4) production and brown adipose tissue (BAT) thermogenesis. Administration of exogenous APOA4 elevates BAT thermogenesis in chow-fed mice, but not high-fat diet (HFD)-fed mice. Chronic feeding of HFD attenuates plasma APOA4 production and BAT thermogenesis in wildtype (WT) mice. In light of these observations, we sought to determine whether steady production of APOA4 could keep BAT thermogenesis elevated, even in the presence of HFD consumption, with an aim toward eventual reduction of body weight, fat mass and plasma lipid levels. Transgenic mice with overexpression of mouse APOA4 in the small intestine (APOA4-Tg mice) produce greater plasma APOA4 than their WT controls, even when fed an atherogenic diet. Thus, we used these mice to investigate the correlation of levels of APOA4 and BAT thermogenesis during HFD consumption. The hypothesis of this study was that overexpression of mouse APOA4 in the small intestine and increased plasma APOA4 production would increase BAT thermogenesis and consequently reduce fat mass and plasma lipids of HFD-fed obese mice. To test this hypothesis, BAT thermogenic proteins, body weight, fat mass, caloric intake, and plasma lipids in male APOA4-Tg mice and WT mice fed either a chow diet or a HFD were measured. When fed a chow diet, APOA4 levels were elevated, plasma triglyceride (TG) levels were reduced, and BAT levels of UCP1 trended upward, while body weight, fat mass, caloric intake, and plasma lipids were comparable between APOA4-Tg and WT mice. After a four-week feeding of HFD, APOA4-Tg mice maintained elevated plasma APOA4 and reduced plasma TG, but UCP1 levels in BAT were significantly elevated in comparison to WT controls; body weight, fat mass and caloric intake were still comparable. After 10-week consumption of HFD, however, while APOA4-Tg mice still exhibited increased plasma APOA4, UCP1 levels and reduced TG levels, a reduction in body weight, fat mass and levels of plasma lipids and leptin were finally observed in comparison to their WT controls and independent of caloric intake. Additionally, APOA4-Tg mice exhibited increased energy expenditure at several time points when measured during the 10-week HFD feeding. Thus, overexpression of APOA4 in the small intestine and maintenance of elevated levels of plasma APOA4 appear to correlate with elevation of UCP1-dependent BAT thermogenesis and subsequent protection against HFD-induced obesity in mice. [ABSTRACT FROM AUTHOR]

Kiwifruit contain many components, some considered beneficial, such as vitamins, phytochemicals and dietary fibre, and others potentially harmful, such as fructose and glucose in fruit sugars. In a 6-week, randomised, crossover study aimed at exploring the net effects of daily consumption of kiwifruit, 23 healthy participants consumed two Actinidia chinensis var. chinensis ‘Zesy002’ (marketed as Zespri™ SunGold™ Kiwifruit) per day as part of their customary diet (intervention) or without kiwifruit (control) as their customary diet for 6 weeks in a cross-over study. Anthropometric data, venous blood, and urine samples were collected at the start and end of the 6-week intervention and control periods for the measurement of physical changes, plasma glucose, insulin, glycated haemoglobin, short-chain fatty acids, blood lipids, uric acid, inflammatory biomarkers, and urinary ascorbic acid. Variables were measured between the start and finish of interventions, and between intervention and control periods. Food diaries were completed on the 3 days before blood sampling to estimate dietary ascorbic acid and dietary fibre intakes. Despite urinary vitamin C and food diaries indicating compliance, and good precision in measurements, there were no appreciable changes in biomarkers during the study, either within or between intervention and control periods, that would indicate a change in health status. Thus, the sizes of any effects of kiwifruit ingestion were too small to become significant under the test conditions used, indicating a high probability that daily ingestion of two SunGold kiwifruit is safe with respect to metabolic health.

Abstract Background Muscular dystrophy (MD) causes muscle wasting and is often lethal in patients due to a lack of proven therapies. In contrast, mouse models of MD are notoriously mild. We have previously shown severe human‐like muscle pathology in mdx [Duchenne MD (DMD)] and dysferlin‐deficient limb‐girdle MD type 2B (LGMD2B) mice by inactivating the gene encoding for apolipoprotein E (ApoE), a lipid transporter synthesized by the liver, brain and adipocytes to regulate lipid and fat metabolism. Having recently established that human DMD is a novel type of primary genetic dyslipidaemia with elevated cholesterol, we sought to determine whether cholesterol could exacerbate the muscle wasting process observed in severe rodent MD. Methods Severe mdx and dysferlin knock‐out mice lacking ApoE were treated with ezetimibe (15 mg/kg/day), a clinically approved drug exhibiting few pleiotropic effects. In separate studies, dietary cholesterol was raised (from 0.2% to 2% cholesterol) in combination with experimental micro‐injury and direct cholesterol injection assays. Muscles were assessed histologically for changes in collagen and adipocyte infiltration and both transcriptomic and cellular changes by RNA‐seq and fluorescence‐activated cell sorting analysis. Results Treatment of severe DMD and LGMD2B mice with ezetimibe completely prevented clinical signs of ambulatory dysfunction (0% incidence vs. 33% for vehicle treatment; P

Patients with non-alcoholic steatohepatitis (NASH) show significantly faster progress in the stages of fibrosis compared to those with non-alcoholic fatty liver (NAFL) disease. The non-invasive diagnosis of NASH remains an unmet clinical need. Preliminary data have shown that sphingolipids, especially ceramides, fatty acids, and other lipid classes may be related to the presence of NASH and the histological activity of the disease. The aim of our study was to assess the association of certain plasma lipid classes, such as fatty acids, acylcarnitines, and ceramides, with the histopathological findings in patients with NASH. The study included three groups: patients with NASH (N = 12), NAFL (N = 10), and healthy [non non-alcoholic fatty liver disease (NAFLD)] controls (N = 15). Plasma samples were collected after 12 h of fasting, and targeted analyses for fatty acids, acylcarnitines, and ceramides were performed. Baseline clinical and demographic characteristics were collected. There was no significant difference in baseline characteristics across the three groups or between NAFL and NASH patients. Patients with NASH had increased levels of several fatty acids, including, among others, fatty acid (FA) 14:0, FA 15:0, FA 18:0, FA 18:3n3, as well as Cer(d18:1/16:0), compared to NAFL patients and healthy controls. No significant difference was found between NAFL patients and healthy controls. In conclusion, patients with NASH exhibited a distinctive plasma lipid profile that can differentiate them from NAFL patients and non-NAFLD populations. More data from larger cohorts are needed to validate these findings and examine possible implications for diagnostic and management strategies of the disease.

The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed, Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius’s health-promoting properties.

We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and p-values were calculated through adaptive permutation tests by the PLINK software, v1.9. Over one-year rosuvastatin therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm < 0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm < 0.05). In conclusion, polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients.

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice. However, the physiological role of continuous infusion of recombinant APOA4 protein in regulating sympathetic activity, thermogenesis, and lipid and glucose metabolism in low-fat-diet (LFD)-fed mice remained elusive. The hypothesis of this study was that continuous infusion of mouse APOA4 protein would increase sympathetic activity and thermogenesis in BAT and subcutaneous inguinal white adipose tissue (IWAT), attenuate plasma lipid levels, and improve glucose tolerance. To test this hypothesis, sympathetic activity, BAT temperature, energy expenditure, body weight, fat mass, caloric intake, glucose tolerance, and levels of BAT and IWAT thermogenic and lipolytic proteins, plasma lipids, and markers of fatty acid oxidation in the liver in mice with APOA4 or saline treatment were measured. Plasma APOA4 levels were elevated, BAT temperature and thermogenesis were upregulated, and plasma triglyceride (TG) levels were reduced, while body weight, fat mass, caloric intake, energy expenditure, and plasma cholesterol and leptin levels were comparable between APOA4- and saline-treated mice. Additionally, APOA4 infusion stimulated sympathetic activity in BAT and liver but not in IWAT. APOA4-treated mice had greater fatty acid oxidation but less TG content in the liver than saline-treated mice had. Plasma insulin in APOA4-treated mice was lower than that in saline-treated mice after a glucose challenge. In conclusion, continuous infusion of mouse APOA4 protein stimulated sympathetic activity in BAT and the liver, elevated BAT thermogenesis and hepatic fatty acid oxidation, and consequently attenuated levels of plasma and hepatic TG and plasma insulin without altering caloric intake, body weight gain and fat mass.

Although brown adipose tissue (BAT) is considered to play a protective role against obesity and type 2 diabetes, the mechanisms of its activation and associations with clinical parameters are not well described. Male adults underwent a 2 h cold exposure (CE) to activate BAT and, based on the results of PET/MRI performed after the CE, were divided into BAT(+) and BAT(−) groups. During the CE procedure, blood samples were collected and alterations in plasma metabolome in both groups were investigated using LC-MS. Additionally, associations between clinical factors and BAT were examined. Moreover, levels of glucose, insulin, leptin, TNF-α, FGF21, and FABP4 were assessed in serum samples. In the BAT(+) group, levels of LPC(17:0), LPE(20:4), LPE(22:4), LPE(22:6), DHA, linoleic acid, and oleic acid increased during CE, whereas levels of sphinganine-phosphate and sphingosine-1-phosphate decreased. Levels of LPE(O-18:0), 9-HpODE, and oleic acid were elevated, while the level of LPE(20:5) was reduced in BAT(+) compared to BAT(−) subjects. AUCs of LPC(18:2), LPC(O-18:2)/LPC(P-18:1), and SM(d32:2) negatively correlated with BAT. In the BAT(+) group, the concentration of FABP4 during and after CE was decreased compared to the basal level. No alterations were observed in the BAT(−) group. In conclusion, using untargeted metabolomics, we proved that the plasma metabolome is affected by cold-induced BAT activation. [ABSTRACT FROM AUTHOR]

Low plasma cholesterol may be associated with preterm birth; however, results are mixed and limited primarily to high-income countries. Our objective was to determine whether maternal plasma lipid concentrations are associated with pregnancy duration. We performed a nested cohort (n = 320) study of pregnant Ghanaian women enrolled in a randomized controlled trial. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride concentrations were analyzed in plasma at ≤20and 36 weeks gestation as continuous variables and also categorized into low, referent, or high (90th percentile). At ≤20 weeks, plasma lipid concentrations were not associated with pregnancy duration. At 36 weeks, total cholesterol and triglyceride concentrations were not associated with pregnancy duration. Higher HDL-C at 36 weeks was associated with a longer pregnancy duration (adjusted β-coefficient ± standard error: 0.05 ± 0.02 days mg-1 /dL, p = .02); pregnancy duration was 5.9 ± 2.0 (mean ± standard error) days shorter among women with low HDL-C compared with the referent group (10th-90th percentile) (p = .02) and 8.6 ± 2.6 days shorter when compared with the high HDL-C group (p = .003). Pregnancy duration was 4.9 ± 2.1 days longer among women with low low-density lipoprotein cholesterol at 36 weeks gestation when compared with the referent group (p = .051). Our data suggest that low HDL-C in the third trimester of pregnancy is associated with a shorter duration of pregnancy in this study population but do not support the hypothesis that low total cholesterol is associated with a shorter pregnancy duration.

We review current knowledge on lipid metabolism changes during pregnancy with special focus on changes in gestational diabetes. In physiological pregnancy, total plasma cholesterol, triglyceride and HDL-cholesterol level rises, the atherogenic index (LDL-cholesterol / HDL-cholesterol remains unchanged. Compared with healthy women, women with GDM show more pronounced signs of mixed dyslipidaemia - increased levels of triglyceride, changes in cholesterol and lipoprotein concentrations with a shift towards greater small dense LDL subtractions, which is typical for insulin resistance states. Dyslipidaemia, particularly hypertriglyceridemia, is thought to be one of the key drivers of foetal macrosomia and that is why measurements of plasma lipids may be valuable in detecting the metabolic abnormality in GDM and in predicting foetal outcome. Dyslipidaemia in GDM is seen as proatherogenic and potentially harmful for the baby and therefore it should be monitored more carefully.

Although a growing number of studies have attempted to uncover the relationship between plasma lipids and the risk of aortic aneurysm (AA), it remains controversial. Meanwhile, the relationship between plasma lipids and the risk of aortic dissection (AD) has not been reported on. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the potential relationship between genetically predicted plasma levels of lipids and the risk of AA and AD. Summary data on the relationship between genetic variants and plasma lipids were obtained from the UK Biobank and Global Lipids Genetics Consortium studies, and data on the association between genetic variants and AA or AD were taken from the FinnGen consortium study. Inverse-variance weighted (IVW) and four other MR analysis methods were used to evaluate effect estimates. Results showed that genetically predicted plasma levels of low-density lipoprotein cholesterol, total cholesterol, or triglycerides were positively correlated with the risk of AA, and plasma levels of high-density lipoprotein cholesterol were negatively correlated with the risk of AA. However, no causal relationship was found between elevated lipid levels and the risk of AD. Our study revealed a causal relationship between plasma lipids and the risk of AA, while plasma lipids had no effect on the risk of AD.

Dietary lipids induce apolipoprotein A4 (APOA4) production and brown adipose tissue (BAT) thermogenesis. Administration of exogenous APOA4 elevates BAT thermogenesis in chow-fed mice, but not high-fat diet (HFD)-fed mice. Chronic feeding of HFD attenuates plasma APOA4 production and BAT thermogenesis in wildtype (WT) mice. In light of these observations, we sought to determine whether steady production of APOA4 could keep BAT thermogenesis elevated, even in the presence of HFD consumption, with an aim toward eventual reduction of body weight, fat mass and plasma lipid levels. Transgenic mice with overexpression of mouse APOA4 in the small intestine (APOA4-Tg mice) produce greater plasma APOA4 than their WT controls, even when fed an atherogenic diet. Thus, we used these mice to investigate the correlation of levels of APOA4 and BAT thermogenesis during HFD consumption. The hypothesis of this study was that overexpression of mouse APOA4 in the small intestine and increased plasma APOA4 production would increase BAT thermogenesis and consequently reduce fat mass and plasma lipids of HFD-fed obese mice. To test this hypothesis, BAT thermogenic proteins, body weight, fat mass, caloric intake, and plasma lipids in male APOA4-Tg mice and WT mice fed either a chow diet or a HFD were measured. When fed a chow diet, APOA4 levels were elevated, plasma triglyceride (TG) levels were reduced, and BAT levels of UCP1 trended upward, while body weight, fat mass, caloric intake, and plasma lipids were comparable between APOA4-Tg and WT mice. After a four-week feeding of HFD, APOA4-Tg mice maintained elevated plasma APOA4 and reduced plasma TG, but UCP1 levels in BAT were significantly elevated in comparison to WT controls; body weight, fat mass and caloric intake were still comparable. After 10-week consumption of HFD, however, while APOA4-Tg mice still exhibited increased plasma APOA4, UCP1 levels and reduced TG levels, a reduction in body weight, fat mass and levels of plasma lipids and leptin were finally observed in comparison to their WT controls and independent of caloric intake. Additionally, APOA4-Tg mice exhibited increased energy expenditure at several time points when measured during the 10-week HFD feeding. Thus, overexpression of APOA4 in the small intestine and maintenance of elevated levels of plasma APOA4 appear to correlate with elevation of UCP1-dependent BAT thermogenesis and subsequent protection against HFD-induced obesity in mice.

Many foods are prepared by deep-frying as this provides unique flavors/textures that improve overall palatability to consumers. Sunflower oil is one of the most widely-used frying oils in the world. However, during frying, fats in the foodstuff are heated to > 150° C and concurrently come into contact with agents found in the air, water, and other foods being cooked at the same time. Since long-term consumption of oxidized/oxidation products can contribute to the development of a variety of pathologies. Used cooking oil has become of increased concern to both health administrators and consumers. Few studies have sought to examine potential immunomodulatory effects from exposures to sunflower oil or its oxidized/oxidation products. To address this gap in knowledge, here, sunflower oil was used to fry potatoes at 190° C, every 30 min; a new 100 g batch of slices was cooked. Frying was performed continuously for 5h/day for 2 and 4 days (10 and 20 h total), and then the parental uncooked oil and each of the used oils were provided to Wistar rats in their diet (at 20% level) for a total of 10 weeks. Measures of body weight\food intake indicated that diets containing the used oils led to slightly reduced food intakes and host weights. Kidney weights were not affected by consumption of the two used oils, but the liver was enlarged in rats fed with the oil treated for 20 h. Evaluation of key lipidserum parameters, i.e., total cholesterol, HDL cholesterol, and triglycerides, revealed a diet-related decrease in each; oxidized fats reduce their concentration compared to fresh fats. Conversely, serum LDL cholesterol levels were increased. Histological analyses indicated that consumption of the oxidized oils caused both kidney (e.g., tubular/glomerular dilation, vascular congestion, inflammation, tubular necrosis) and liver (e.g., vascular congestion, inflammation, necrosis) damages. Assessments of host immune function, i.e., ability to form antibody to ovalbumin (OVA) challenge, indicated that in rats fed the used oil, there were significant decreases in serum anti-OVA antibody levels. This suggested that host immunocompetence could be compromised as a result of long-term consumption of a diet containing a relatively high (i.e., 20%) content of used sunflower oils. [ABSTRACT FROM AUTHOR]

Hypothyroidism increases the incidence of gestational diabetes mellitus (GDM) but the mechanisms responsible are unknown. This study aimed to assess the pathophysiological mechanisms by which hypothyroidism leads to glucose intolerance in pregnancy. Hypothyroidism was induced in female Sprague-Dawley rats by adding methimazole (MMI) to drinking water at moderate (MOD, MMI at 0.005% w/v) and severe (SEV, MMI at 0.02% w/v) doses from 1 week before pregnancy and throughout gestation. A nonpregnant cohort received the same dose for the same duration but were not mated. On gestational day 16 (GD16), or nonpregnant day 16 (NP16), animals were subjected to an intraperitoneal glucose tolerance test. Tissues and blood samples were collected 4 days later. Hypothyroidism induced a diabetic-like phenotype by GD16 in pregnant females only. Pregnant MOD and SEV females had reduced fasting plasma insulin, less insulin following a glucose load, and altered expression of genes involved in insulin signaling within skeletal muscle and adipose tissue. Hypothyroidism reduced rat placental lactogen concentrations, which was accompanied by reduced percentage β-cell cross-sectional area (CSA) relative to total pancreas CSA, and a reduced number of large β-cell clusters in the SEV hypothyroid group. Plasma triglycerides and free fatty acids were reduced by hypothyroidism in pregnant rats, as was the expression of genes that regulate lipid homeostasis. Hypothyroidism in pregnant rats results in a diabetic-like phenotype that is likely mediated by impaired β-cell expansion in pregnancy. This pregnancy-specific phenomenon is likely due to reduced placental lactogen secretion. [ABSTRACT FROM AUTHOR]

Background: Red rice koji (RRK), prepared by growing Monascus species on steamed rice, has been reported to lower blood glucose levels in diabetic animal models. However, the action mechanism is not yet completely understood. Objective: The objective of this study was to examine the mechanism underlying the hypoglycemic action of RRK extract in two diabetic animal models: the insulin-deficiency mice, where the insulin deficiency was induced by streptozotocin (STZ), and insulin-resistance mice, where the insulin resistance was induced by a high-fat diet (HFD). Design: Low (12.5 mg/kg body weight [BW]) and high (50.0 mg/kg BW) doses of RRK extract were orally administered to the mice for 10 successive days (0.25 mL/day/mouse). The protein expression levels of glucose transporter type 4 (GLUT4) in the skeletal muscle and glucose transporter type 2 (GLUT2) in the liver were measured. Blood glucose (BG) levels of STZ-treated mice in insulin tolerance test (ITT) and BG and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test (IPGTT) were investigated. Results: In the STZ-treated mice, oral administration of RRK extract lowered BG levels and food intake but increased plasma 1,5-anhydroglucitol level. Moreover, the RRK extract lowered the BG levels of STZ-treated mice as measured by ITT. In the HFD-fed mice, we confirmed that the orally administered RRK extract lowered the BG and the homeostasis model assessment index for insulin resistance. Furthermore, the RRK extract lowered the BG and insulin levels of HFD-fed mice in IPGTT. Regarding the protein levels of GLUT, the orally administered RRK extract increased the GLUT4 level in the skeletal muscle; however, the RRK extract did not alter the GLUT2 level in the liver of either the STZ-treated or the HFD-fed mice. Discussion: Our study demonstrates that RRK extract can improve impaired glucose tolerance in mouse models of diabetes by enhancing GLUT4 expression in skeletal muscle. Conclusion: These results suggest that RRK extract could potentially be a functional food for the treatment of diabetes mellitus.

Abstract Background Epigenetics can contribute to lipid disorders in obesity. The DNA methylation pattern can be the cause or consequence of high blood lipids. The aim of the study was to investigate the DNA methylation profile in peripheral leukocytes associated with elevated LDL-cholesterol level in overweight and obese individuals. Methods To identify the differentially methylated genes, genome-wide DNA methylation microarray analysis was performed in leukocytes of obese individuals with high LDL-cholesterol (LDL-CH, ≥ 3.4 mmol/L) versus control obese individuals with LDL-CH,

Abstract Background Recently, some studies claim that adipokines may modulate plasma lipids. More interestingly, the ADRB3 Trp64Arg polymorphism may regulate adipokines and play an essential role in lipids metabolism. This study aims to clarify the associations of ADRB3 Trp64Arg polymorphism with plasma adipokines and lipid levels. Methods Twenty-two studies (5527 subjects) and 121 studies (54,059 subjects) were respectively identified for the association analyses of adipokines and lipids. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate the strength of the Trp64Arg variant in adipokines and plasma lipids. All results were recalculated after eliminating the studies with heterogeneity. Results The carriers of the C allele (Arg at 64th position was encoded by the C allele) had higher levels of leptin and lower levels of adiponectin than the non-carriers. The carriers of the C allele had higher levels of triglycerides (TG), total cholesterol (TC), and lower levels of high-density lipoprotein cholesterol (HDL-C) than the non-carriers. Subgroup analysis certified an ethnicity (Asians), disease status (obesity), and gender (females) specific association. Sensitivity analysis indicated that the analysis results were robust and stable. Meta-regression indicated that obesity was related to adiponectin. Conclusions The C allele carriers of Trp64Arg polymorphism had a slight but significant influence on lipid levels, and the remarkable effects specific existed in obese Asian women. The associations of Trp64Arg polymorphism with dyslipidemia may partly be mediated by the effect of this polymorphism on adipokines. The association of Trp64Arg polymorphism with obesity may partly be mediated by the effect of this polymorphism on adipokines. The C allele carriers had abnormal levels of adipokines and lipids, and it indicated that the Trp64Arg polymorphism might represent a genetic risk factor for coronary artery disease (CAD).

With the development of designed materials and structures, a wide array of micro/nanomachines with versatile functionalities are employed for specific sensing applications. Here, we demonstrated a magnetic propelled microdimer-based point-of-care testing system, which can be used to provide the real-time data of plasma glucose and lipids relying on the motion feedback of mechanical properties. On-demand and programmable speed and direction of the microdimers can be achieved with the judicious adjustment of the external magnetic field, while their velocity and instantaneous postures provide estimation of glucose, cholesterol, and triglycerides concentrations with high temporal accuracy. Numerical simulations reveal the relationship between motility performance and surrounding liquid properties. Such technology presents a point-of-care testing (POCT) approach to adapt to biofluid measurement, which advances the development of microrobotic system in biomedical fields.

Background and Objective: Hemorrhagic stroke, characterized by acute bleeding due to cerebrovascular lesions, is associated with plasma lipids and endothelial damage. The causal relationship between genetic plasma lipid levels and hemorrhagic stroke remains unclear. This study employs a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between plasma lipid profiles with different fatty acid chains and the risk of intracerebral and subarachnoid hemorrhage, the two main subtypes of hemorrhagic stroke., Methods: The datasets for exposure and outcome summary statistics were obtained from publicly available sources such as the GWAS Catalog, IEU OpenGWAS project, and FinnGen. The two-sample MR analysis was employed to initially assess the causal relationship between 179 plasma lipid species and the risk of intracerebral and subarachnoid hemorrhage in the Finnish population, leading to the identification of candidate lipids. The same methods were applied to reanalyze data from European populations and conduct a meta-analysis of the candidate lipids. The Inverse Variance Weighting (IVW) method served as the primary analysis for causal inference, with additional methods used for complementary analyses. Sensitivity analysis was conducted to clarify causal relationships and reduce biases., Results: Two analyses using Mendelian randomization were performed, followed by meta-analyses of the results. A causal relationship was established between 11 specific lipid species and the occurrence of intracerebral hemorrhage within the European population. Additionally, 5 distinct lipid species were associated with subarachnoid hemorrhage. Predominantly, lipids with linoleic acid and arachidonic acid side chains were identified. Notably, lipids containing arachidonic acid chains (C20:4) such as PC 18:1;0&#95;20:4;0 consistently showed a decreased risk of both intracerebral hemorrhage [ p  < 0.001; OR(95% CI) = 0.892(0.835-0.954)] and subarachnoid hemorrhage [ p  = 0.002; OR(95% CI) = 0.794(0.689-0.916)]. Conversely, lipids with linoleic acid chains (C18:2) were associated with an increased risk of intracerebral hemorrhage., Conclusion: This study identifies a potential causal relationship between lipids with different fatty acid side chains and the risk of intracerebral and subarachnoid hemorrhagic stroke, improving the understanding of the mechanisms behind the onset and progression of hemorrhagic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhu and Shi.)

Background: Menopause signifies the eternal termination of menstruation in women as a consequence of ovarian action loss, typically occurring around the age of 51 years. Cardiovascular disease is the leading cause of death among post-menopausal women, which may be due to lower levels of estrogen and lipid profile. The present study was undertaken to evaluate serum estrogen and lipid profile status to assess the risk of atherosclerosis in both pre- and post-menopausal women., Objectives: The objective of this study is to explore the relationship between estrogen and lipid levels of women in pre- and post-menopausal stages., Methodology: A comparative cross-sectional study was conducted at Railway General Hospital Rawalpindi. A total of 100 participants were included of which 50 were pre-menopausal and 50 were post-menopausal women. Laboratory examination and questionnaires from the study population were used for data collection. Through the enzymatic method, serum cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) were assessed. Serum very low-density lipoprotein (VLDL) levels were calculated via Friedwald's components VLDL=TG/5.0. An enzyme-linked immunosorbent assay kit was used for estrogen measurement. For statistical analysis, Student's t-test and the Pearson correlation test were used., Results: Women after menopause have significantly high serum cholesterol, low-density lipoproteins, VLDLs, and triglycerides while HDL-c levels were significantly low ( P <0.001). Levels of estrogen were low in post-menopausal females ( P <0.001) as compared to menstruating women. Estrogen with HDL concentrations showed a positive correlation with an r value of 0.08556 while LDL levels showed a negative correlation with a r value of -0.26219., Conclusion: This comparative study explores the relationship between estrogen and lipid levels in pre- and post-menopausal women. Low estrogen with changed lipid variables was observed. Decreased cardiovascular protective HDL-c marks that menopause is a phase that acts as an independent risk factor for atherosclerosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Research Ethical Committee of Riphah College of Rehabilitation Sciences, Riphah International University issued approval Riphah/RCRAHS-ISB/REC/BS-MLT-G/10008. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Chaudhry et al.)

Objectives: To investigate the association of plasma LPS mass with mortality and inflammation in patients with peritonitis-induced septic shock (SS).Design: Longitudinal endotoxin and inflammatory parameters in a multicentric cohort of SS.Patients: Protocolized post-operative parameters of 187 SS patients collected at T1 (12 h max post-surgery) and T4 (24 h after T1).Intervention:Post-hoc analysis of ABDOMIX trial.Measurements and Results: Plasma concentration of LPS mass as determined by HPLC-MS/MS analysis of 3-hydroxymyristate, activity of phospholipid transfer protein (PLTP), lipids, lipoproteins, IL-6, and IL-10. Cohort was divided in low (LLPS) and high (HLPS) LPS levels. The predictive value for mortality was tested by multivariate analysis. HLPS and LLPS had similar SAPSII (58 [48.5; 67]) and SOFA (8 [6.5; 9]), but HLPS showed higher death and LPS to PLTP ratio (p < 0.01). LPS was stable in HLPS, but it increased in LLPS with a greater decrease in IL-6 (p < 0.01). Dead patients had a higher T1 LPS (p = 0.02), IL-6 ( median, the risk of death in HLPS (38%) was higher than in LLPS (24%; p < 0.01). The 28-day death was associated only with SAPSII (OR 1.06 [1.02; 1.09]) and HLPS (OR 2.47 [1; 6.11]) in the multivariate model. In HLPS group, high PLTP was associated with lower plasma levels of IL-6 (p = 0.02) and IL-10 (p = 0.05).Conclusions: Combination of high LPS mass concentration and high SAPS II is associated with elevated mortality in peritonitis-induced SS patients.

Objective: Dyslipidemia, a disorder in the levels of cholesterol or lipoproteins in the plasma, is a feature of atherosclerosis, leading to cardiovascular disease. The objective of this study was to evaluate whether Tanerella forsythia and Treponema denticola are related to reduced levels of antiatherogenic high density lipoprotein (HDL). Method and Materials: In this cross-sectional study, 108 patients were invited to participate. The diagnosis of chronic periodontitis and the diagnosis of adipose tissue disorders were made based on criteria previously defined. The presence of T forsythia and T denticola was detected by polymerase chain reaction. Results: A total of 61 women and 19 men with chronic periodontitis, and 18 women and 10 men without periodontitis were studied. The serum levels of total cholesterol and low density lipoprotein were similar in both groups. Inversely, the levels of triglycerides (TG) were higher in periodontitis patients compared to subjects without periodontitis (178 mg/dL vs 165 mg/dL; P < .05), and the levels of HDL were lower (44 mg/dL vs 50 mg/dL; P < .05), respectively. The presence of T denticola was associated with low levels of HDL in periodontitis patients after adjustment for possible confounders (OR, 3.03; 95% CI, 1.2–7.2). Conclusion: Higher levels of TG and lower levels of HDL were associated with the presence of T denticola in chronic periodontitis. These results may suggest that the presence of T denticola could reduce the antiatherogenic potency of HDL and may increase the risk for cardiovascular disease in patients with chronic periodontitis. [ABSTRACT FROM AUTHOR]

Background and Aims: In the present study, we aimed to compare the clinical and coronary angiography features between South Asian and Caucasian patients with Acute Coronary Syndrome (ACS). In particular, we focused our analysis on the evaluation of recent cardiovascular risk markers, such as remnant cholesterol, corresponding to all plasma cholesterol minus HDL-C (high-density lipoprotein cholesterol) and LDL-C (low-density lipoprotein cholesterol), and the Monocyte-to-HDL-cholesterol ratio. We also compared values of several lipoprotein ratios and the Platelet-to-lymphocyte ratio, accurate predictors of coronary events and coronary artery disease.Methods and Results: We recruited 40 South Asian and 40 Caucasian patients admitted for ACS. Data were collected by consulting patients' medical records. We used Chi-square test and Student's t-test to analyse qualitative and quantitative variables, respectively. South Asian patients, compared to Caucasians, showed higher mean values of the parameters analysed: remnant cholesterol (32.6 ± 17 vs 26.5 ± 9.6), Monocyte-to-HDL-cholesterol ratio (26.4 ± 48.7 vs 16.5 ± 8.3), Platelet-to-lymphocyte ratio (124.7 ± 130.7 vs 120.5 ± 58.8). Moreover, higher mean values of several lipoprotein ratios were also found in South Asian patients compared to the control group. However, statistical significance was not reached for any of these differences observed.Conclusions: The evaluation of the parameters analysed in this study might provide accurate information regarding the cardio-metabolic risk in South Asian patients. However, further studies with larger samples are needed to obtain more significant results. [ABSTRACT FROM AUTHOR]

Choline plays a crucial role in lipid metabolism for fish, and its deficiency in aquafeed has been linked to compromised health and growth performance. A 56-d experiment was conducted to examine the effects of dietary choline on lipid composition, histology and plasma biochemistry of yellowtail kingfish (Seriola lalandi; YTK; 156 g initial body weight). The dietary choline content ranged from 0·59 to 6·22 g/kg diet. 2-Amino-2-methyl-1-propanol (AMP) (3 g/kg) was added to diets, except for a control diet, to limit de novo choline synthesis. The results showed that the liver lipid content of YTK was similar among diets containing AMP and dominated by NEFA. In contrast, fish fed the control diet had significantly elevated liver TAG. Generally, the SFA, MUFA and PUFA content of liver lipid in fish fed diets containing AMP was not influenced by choline content. The SFA and MUFA content of liver lipid in fish fed the control diet was similar to other diets except for a decrease in PUFA. The linear relationship between lipid digestibility and plasma cholesterol was significant, otherwise most parameters were unaffected. When AMP is present, higher dietary choline reduced the severity of some hepatic lesions. The present study demonstrated that choline deficiency affects some plasma and liver histology parameters in juvenile YTK which might be useful fish health indicators. Importantly, the present study elucidated potential reasons for lower growth in choline-deficient YTK and increased the knowledge on choline metabolism in the fish. [ABSTRACT FROM AUTHOR]

We examined the relationships between the dietary inflammatory index (DII®), dietary habits and cardiovascular risk factor profiles in people with type 2 diabetes mellitus (T2DM). Energy-adjusted DII (E-DII™) scores were calculated from a Food Frequency Questionnaire in 2568 T2DM patients from different parts of Italy. Analyses were conducted according to quartiles of sex-specific E-DII scores. Higher, more pro-inflammatory, (quartile 4) E-DII scores were associated with overall poor quality of the diet characterised by higher content of refined carbohydrates, added sugars, saturated fat and cholesterol and lower unsaturated fat, fibre and polyphenols compared to quartile 1. Higher E-DII scores also were associated with higher waist circumference (105.4 vs. 103.5 cm; p = 0.002), triglycerides (154.6 vs. 146.1 mg/dL; p = 0.005), diastolic blood pressure (80.05 vs. 78.6 mmHg; p = 0.04) and lower HDL-cholesterol (45.3 vs. 47.4 mg/dL; p = 0.04). In conclusion, E-DII is a potent marker of overall quality of the diet and is associated with an unfavourable cardiovascular risk factor profile. [ABSTRACT FROM AUTHOR]