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Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115 mg/dl, high-density lipoprotein (HDL) <40 mg/dl for males, or HDL <50 mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150 mg/dl. At the follow-up, a variation of ±40 mg/dl for LDL, ±6 mg/dl for HDL, and ±50 mg/dl for triglycerides was considered relevant. Athletes with follow-up <10 months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6 months. Mean age was 27.2 ± 4.8 years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Purpose: Previous literature has demonstrated the mediating role of adiposity in the association between cardiorespiratory fitness (CRF) and cardiometabolic risk as well as the potential role of CRF in attenuating the adverse consequences associated with excess weight. This study aimed to evaluate the mediating role of CRF and adiposity in the possible association with cardiometabolic risk. Method: Observational 3-year longitudinal study that included 420 children and adolescents (10.50 [2.05] y of age at baseline; 56.2% girls). Body mass index (BMI) was calculated, and CRF was evaluated using field assessments. A clustered cardiometabolic risk score (cMetS) was calculated from glucose, systolic blood pressure, total cholesterol/high-density lipoprotein cholesterol ratio, and triglycerides z scores. Analyses evaluated the mediating role of BMI in the association between CRF and cMetS as well as whether CRF mediated the association between BMI and cMetS. Results: BMI at baseline was directly associated with the cMetS at follow-up (0.102; 95% confidence interval, 0.020 to 0.181), independently of CRF, whereas CRF was only indirectly associated with cMetS at follow-up through BMI (−0.036; 95% confidence interval, −0.070 to −0.009), meaning that the association between CRF and cMetS was explained via the mediation role of BMI. Conclusions: BMI presented direct association with cMetS, whereas CRF exhibited indirect association with cMetS mediated via BMI. [ABSTRACT FROM AUTHOR]

Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (-Fe). Cells grown in -Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 adults with PTSD and 40 trauma-exposed non-PTSD individuals (n = 20/sex/condition; 19-39 years old). Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, ~ 90 measures were collected, on sleep, and mental and physical health indices. Poorer sleep quality was associated with greater PTSD severity in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 lipid subclasses. After adjusting for BMI and sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The correlations between triglycerides and ceramide metabolites with cholesterol metabolites and systolic blood pressure were dependent upon sex and PTSD status. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher body mass may have contributed to changes in the lipidome found in PTSD.

Apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia in mice and humans. For years, the cause remained a mystery, but the mechanisms have now come into focus. Here, we review progress in defining APOA5s function in plasma triglyceride metabolism. Biochemical studies revealed that APOA5 binds to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppresses its ability to inhibit the activity of lipoprotein lipase (LPL). Thus, APOA5 deficiency is accompanied by increased ANGPTL3/8 activity and lower levels of LPL activity. APOA5 deficiency also reduces amounts of LPL in capillaries of oxidative tissues (e.g., heart, brown adipose tissue). Cell culture experiments revealed the likely explanation: ANGPTL3/8 detaches LPL from its binding sites on the surface of cells, and that effect is blocked by APOA5. Both the low intracapillary LPL levels and the high plasma triglyceride levels in Apoa5-/- mice are normalized by recombinant APOA5. Carboxyl-terminal sequences in APOA5 are crucial for its function; a mutant APOA5 lacking 40-carboxyl-terminal residues cannot bind to ANGPTL3/8 and lacks the ability to change intracapillary LPL levels or plasma triglyceride levels in Apoa5-/- mice. Also, an antibody against the last 26 amino acids of APOA5 reduces intracapillary LPL levels and increases plasma triglyceride levels in wild-type mice. An inhibitory ANGPTL3/8-specific antibody functions as an APOA5-mimetic reagent, increasing intracapillary LPL levels and lowering plasma triglyceride levels in both Apoa5-/- and wild-type mice. That antibody is a potentially attractive strategy for treating elevated plasma lipid levels in human patients.

To support in vivo and in vitro studies of intravascular triglyceride metabolism in mice, we created rat monoclonal antibodies (mAbs) against mouse LPL. Two mAbs, mAbs 23A1 and 31A5, were used to develop a sandwich ELISA for mouse LPL. The detection of mouse LPL by the ELISA was linear in concentrations ranging from 0.31 ng/ml to 20 ng/ml. The sensitivity of the ELISA made it possible to quantify LPL in serum and in both pre-heparin and post-heparin plasma samples (including in grossly lipemic samples). LPL mass and activity levels in the post-heparin plasma were lower in Gpihbp1-/- mice than in wild-type mice. In both groups of mice, LPL mass and activity levels were positively correlated. Our mAb-based sandwich ELISA for mouse LPL will be useful for any investigator who uses mouse models to study LPL-mediated intravascular lipolysis.

Several genetic risk factors for Alzheimers disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells1. However, the relationship between lipid metabolism in glia and Alzheimers disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimers disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimers disease having the APOE4/4 genotype. In human induced pluripotent stem cell-derived microglia, fibrillar Aβ induces ACSL1 expression, triglyceride synthesis and lipid droplet accumulation in an APOE-dependent manner. Additionally, conditioned media from lipid droplet-containing microglia lead to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for Alzheimers disease with microglial lipid droplet accumulation and neurotoxic microglia-derived factors, potentially providing therapeutic strategies for Alzheimers disease.

Circulating levels of the soluble ligand-binding ectodomain of the LDL receptor (sLDLR) that is proteolytically cleaved from the cell surface have been shown to correlate with plasma triglycerides, but the lipid and lipoprotein effects of longitudinal changes in sLDLR have not been examined. We sought to assess associations between changes in sLDLR and detailed lipoprotein measurements between baseline and 6 months in participants in the DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) weight loss trial who were randomly assigned to the low-fat (n = 225) or low-carbohydrate (n = 236) diet arms. sLDLR was assayed using a proteomic procedure, lipids and apoprotein (apo) B and apoAI were measured by standard assays, and lipoprotein particle subfractions were quantified by ion mobility methodology. Changes in sLDLR were significantly positively associated with changes in plasma cholesterol, triglycerides, apoB, large-sized and medium-sized VLDL, and small and very small LDL, and inversely with changes in large LDL and HDL. The lipoprotein subfraction associations with sLDLR were independent of age, sex, diet, and BMI, but all except for large LDL were reduced to insignificance when adjusted for triglyceride change. Principal component analysis identified three independent clusters of changes in lipoprotein subfractions that accounted for 78% of their total variance. Change in sLDLR was most strongly correlated with change in the principal component that was loaded positively with large VLDL and small and very small LDL and negatively with large LDL and HDL. In conclusion, sLDLR is a component of a cluster of lipids and lipoproteins that are characteristic of atherogenic dyslipidemia.

BACKGROUND: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. METHODS AND RESULTS: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. CONCLUSIONS: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR)

Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of β3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Although a high amount of brown adipose tissue (BAT) is associated with low plasma triglyceride concentration, the mechanism responsible for this relationship in people is not clear. Here, we evaluate the interrelationships among BAT, very-low-density lipoprotein triglyceride (VLDL-TG), and free fatty acid (FFA) plasma kinetics during thermoneutrality in women with overweight/obesity who had a low (

Background & aimsPathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease.MethodsUsing individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies.ResultsEligible studies numbered 9 (N = 597). The relationship between PDFF and histology was predominantly linear (r = 0.85 [95% CI, 0.80-0.89]), and their values approximately coincided at 5% steatosis. Above 5% and towards higher levels of steatosis, absolute values of the methods diverged markedly, with histology exceeding PDFF by up to 3.4-fold. On average, 100% histological steatosis corresponded to a PDFF of 33.0% (29.5-36.7%). Targeting at a specificity of 90%, optimal PDFF thresholds to predict histological steatosis grades were ≥5.75% for ≥S1, ≥15.50% for ≥S2, and ≥21.35% for S3. Hepatocytes comprised 58 ± 5% of liver cells, which may partly explain the lower values of PDFF vs. histology.ConclusionsHistological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values.Impact and implicationsMagnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.

The structure and composition of mantle tissue from red abalone Haliotis rufescens were studied in relation to pearl farming. Histological (hematoxylin-eosin) and histochemical (PAS AJcian Blue. Sudan Black. Dahl's) tools were used to determine variations in the glycogen index, lipid index, and calcium coverage index of mantle tissue as a function of seasonality (cold and warm period) and body region (dorsal, central, ventral). Anatomically, only two well-developed and functional mantle folds (inner and outer) were observed across the marginal zone, together with a poorly developed, and presumably, rudimentary fold with the same cellular morphology as the inner fold. The inner mantle epithelium stored significantly higher concentrations of glycogen and mucins, triglycerides, and calcium than the outer epithelium. This pattern occurred significantly more during the cold season than during the warm season. Mucins from mantle tissue not only regulate crystal nucleation and orientation during biomineralization, but also give the inner nacreous layer its luster and color. High concentrations of lipids in mantle tissue could help compensate for the energy loss caused by the wound-healing processes associated with mantle tissue removal and seeding, which are stressful and energetically costly. The absorption of calcium ions from the environment to integrate a mierolaminate of calcareous compounds gives the shell its structural properties of hardness and strength. An approach with molecularultrastructural tools is recommended to broaden the understanding of mantle tissue regionalization and its relationship to pearl sac formation, which may help increase pearl yield and quality in H. rufescens. KEY WORDS: abalone, calcium, lipids, mantle tissue, nacre, pearls, INTRODUCTION In most molluscan classes, mantle tissue is responsible for forming a hard calcareous shell from elements and ions taken from the environment. This process, known as biomineralization, provides the [...]

Background: The benefits of physical activity in health outcomes are well established. However, recent evidence suggests that benefits may differ by domain and population. Thus, we aimed to investigate the prospective association of occupational (OPA) and leisure-time physical activity (LTPA) with cardiovascular risk factors. Methods: In 1982, the maternity hospitals of Pelotas were visited daily; those live births whose families lived in urban areas were evaluated, and their mothers were later interviewed (n = 5914). In the 2004/5 follow-up (23 y old), both OPA and LTPA were measured in 4295 participants using their respective sections of the International Physical Activity Questionnaire. In the 2012 follow-up (30 y old), the following cardiovascular risk factors were collected: high-density lipoprotein (in milligrams per deciliter), low-density lipoprotein (in milligrams per deciliter), triglycerides (in milligrams per deciliter), glucose (in milligrams per deciliter), and blood pressure (in millimeters of mercury). Multivariable linear regressions were performed to evaluate associations between OPA and LTPA with these specific cardiovascular risk factors. Results: In total, 3241 participants were analyzed. Our main findings suggest that there was no association between OPA and LTPA with high- and low-density lipoprotein. There were inverse associations between OPA and lower levels of triglycerides among males (β = −0.002; 95% confidence interval, −0.003 to −0.000) and positive associations between LTPA and higher levels of diastolic blood pressure among females (β = 0.111; 95% confidence interval, 0.005–0.216). Conclusion: In conclusion, our findings suggest that there was no association, or association with limited clinical relevance, of OPA and LTPA with cardiovascular risk factors in early adulthood. [ABSTRACT FROM AUTHOR]

We designed to evaluate the effects of resistance elastic band exercises (REBEs) on cardiometabolic/obesity-related biomarkers in older females with osteosarcopenic obesity. Sixty-three patients (aged 65–80 years) with osteosarcopenic obesity and a body mass index exceeding 30 kg/m2 were enrolled in the study. The participants were randomly assigned to either an experimental group (REBE, n = 32) or a usual care group (n = 31). The experimental group completed a 12-week REBE program, three times a week and 60 min per session. There were decreases in lipid accumulation product (p =.033), visceral adipose index (p =.001), triglyceride-glucose-body mass index (p =.034), and atherogenic index of plasma (p =.028) in the experimental group compared with the usual care group. Our findings highlight the importance of an REBE program in improving combined cardiometabolic/obesity-related indices in older women with osteosarcopenic obesity. The incorporation of an REBE program may benefit individuals who are unable to tolerate or participate in more strenuous exercise programs. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown significant associations between individual fat-soluble vitamins (FSVs) and metabolic syndromes (MetS). However, evidence on the multiple FSVs co-exposure and MetS odds is limited. Given that individuals are typically exposed to different levels of FSVs simultaneously, and FSVs can interact with each other. It's necessary to explore the association between multiple FSVs co-exposure and MetS odds. This study aims to address this gap in general U.S. adults aged ≥ 20 years. Methods: We conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Surveys (NHANESs) 2003–2006 and 2017–2018. Three FSV, including vitamin A (VA), vitamin E (VE), and vitamin D (VD), and MetS diagnosed according to the ATP III guidelines were selected as exposure and outcome, respectively. Multivariable-adjusted logistic model was used to explore the associations of individual FSV exposure with MetS odds and MetS components. Restricted cubic splines were performed to explore the dose–response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple FSVs co-exposure with MetS odds and MetS components. Results: The presented study included a total of 13,975 individuals, with 2400 (17.17%) were diagnosed with MetS. After adjusting for various confounders, a positive linear pattern was observed for serum VA and VE and MetS associations. Serum VD was found to be negatively associated with MetS in a linear dose–response way. For each component of MetS, higher serum VA and VE were associated with higher triglyceride and high-density lipoprotein; higher serum VD was negatively associated with triglyceride, blood pressure, and fasting plasma glucose. MetS odds increased by 15% and 13%, respectively, in response to one quartile increase in FSVs co-exposure index (qgcomp) in the conditional model (OR = 1.15, 95%CI: 1.06, 1.24) and the marginal structural model (OR = 1.13, 95%CI: 1.06, 1.20). Besides, co-exposure to VA, VE, and VD was positively associated with triglyceride, high-density lipoprotein, and blood pressure levels. Conclusion: Findings in the present study revealed that high serum VA and VE levels were associated with elevated MetS odds, while serum VD was inversely associated with MetS odds. FSVs co-exposure was positively associated with MetS odds. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsDiscussionSome anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy.Diet-naïve adults with epilepsy who began MAD were divided into three groups based on ASM use: EIASMs, non-EIASMs, and those on no ASMs. Demographic information, epilepsy-specific clinical history, anthropometrics and lipid values were obtained through retrospective chart review at baseline and after a minimum of 12 months of MAD use.Forty-two adults on MAD had baseline and follow up 12-month lipid outcomes. There was a significant increase in median levels of TC, LDL, non-HDL, and HDL after 12 months of MAD use. There was no change in median levels of TG. When separated according to ASM category, adults on non-EIASMs showed significant elevations in TC, HDL, and LDL after 12 months of MAD use. In contrast, adults on EIASMs only showed a significant increase in HDL after 12 months of MAD use.The increase in atherogenic cholesterol levels observed after 12 months of MAD use was most pronounced in adults with epilepsy on non-EIASMs and not observed in adults with epilepsy on EIASMs despite a higher proportion of abnormal cholesterol levels at baseline in those on EIASMs. [ABSTRACT FROM AUTHOR]

In this investigation, we detail the synthesis of silver nanoparticles (AgNPs) via a precise chemical vacuum deposition (CVD) methodology, aimed at augmenting the analytical performance of laser desorption/ionization mass spectrometry (LDI-MS) for the detection of low-molecular-weight analytes. Employing a precursor supply rate of 0.0014 mg/s facilitated the formation of uniformly dispersed AgNPs, characterized by SEM and AFM to have an average diameter of 33.5 ± 1.5 nm and a surface roughness (Ra) of 11.8 nm, indicative of their homogeneous coverage and spherical morphology. XPS and SEM-EDX analyses confirmed the metallic silver composition of the nanoparticles with Ag peak splitting, reflecting the successful synthesis of metallic Ag. Comparative analytical evaluation with traditional MALDI matrices revealed that AgNPs significantly reduce signal suppression, thereby enhancing the sensitivity and specificity of LDI-MS for low-molecular-weight compounds such as triglycerides, saccharides, amino acids, and carboxylic acids. Notably, the application of AgNPs demonstrated a superior linear response for triglyceride signals with regression coefficients surpassing 0.99, markedly outperforming conventional matrices. The study further extends into quantitative analysis through nanoparticle-based laser desorption/ionization (NALDI), where AgNPs exhibited enhanced ionization efficiency, characterized by substantially lower limits of detection (LOD) and quantification (LOQ) for tested standards. Particular attention was paid to lipids with a detailed examination of their fragmentation pathways. These results highlight the significant potential of AgNPs synthesized via CVD to transform the analytical detection and quantification of low-molecular-weight compounds using NALDI. This approach offers a promising avenue for expanding the scope of analytical applications in mass spectrometry and introducing innovative methodologies for enhanced precision and sensitivity. [ABSTRACT FROM AUTHOR]

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P <.05). Subjects with DR had significantly higher triglyceride concentrations (P <.05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P <.05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. Plain Language Summary: Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein (Lp(a)) levels are associated with increased risk of atherosclerotic processes and cardiovascular events in adults. The amount of Lp(a) is mainly genetically determined. Therefore, it is important to identify individuals with elevated Lp(a) as early as possible, particularly if other cardiovascular risk factors are present. The purpose of the study was to investigate whether, in a population of children and adolescents already followed for the presence of one or more cardiovascular risk factors (elevated blood pressure (BP), and/or excess body weight, and/or dyslipidemia), the measurement of Lp(a) can be useful for better stratifying their risk profile. Methods: In a sample of 195 children and adolescents, height, body weight, waist circumference and systolic (SBP) and diastolic (DBP) BP were measured. Body Mass Index (BMI) and SBP and DBP z-scores were calculated. Plasma Lp(a), total cholesterol, high-density lipoprotein (HDL), triglycerides, glucose, insulin, uric acid and creatinine were assessed. Low-density lipoprotein (LDL) cholesterol was calculated with the Friedewald formula. High Lp(a) was defined as ≥ 75 nmol/L and high LDL cholesterol as ≥ 3.37 mmol/L. Results: Our sample of children and adolescents (54.4% males, mean age 11.5 years) had median LDL cholesterol and Lp(a) values equal to 2.54 (interquartile range, IQR: 2.07–3.06) mmol/L and 22 (IQR: 7.8–68.6) nmol/L respectively. 13.8% of children had LDL cholesterol ≥ 3.37 mmol/L and 22.6 Lp(a) values ≥ 75 nmol/L. Lp(a) values were higher in children of normal weight than in those with excess weight (p = 0.007), but the difference disappeared if normal weight children referred for dyslipidemia only were excluded from the analysis (p = 0.210). 69.4% of children had normal Lp(a) and LDL cholesterol values and only 6.2% showed both elevated Lp(a) and LDL cholesterol levels. However, 16.6% of the sample, despite having normal LDL cholesterol, had elevated Lp(a) values. Multivariable analyses showed a significant association of LDL cholesterol both with Lp(a) values, and with the presence of elevated Lp(a) levels. For each mmol/L increase in LDL cholesterol the risk of having an elevated Lp(a) value increased by 73%. There was an inverse correlation between BMI z-score and Lp(a). Neither BP z-scores, nor other biochemical parameters were associated with Lp(a). Conclusions: In our population more than one out of five children had elevated Lp(a) values, and in about 17% of children elevated Lp(a) values were present in the absence of increased LDL cholesterol. Our results suggest that Lp(a) measurement can be useful to better define the cardiovascular risk profile in children and adolescents already followed for the presence of other cardiovascular risk factors such as elevated BP, excess body weight and high LDL cholesterol. [ABSTRACT FROM AUTHOR]

Background: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. Methods: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. Results: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. Conclusions: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity. [ABSTRACT FROM AUTHOR]

The correlation between diabetes and coronary artery disease (CAD) is well established. Insulin resistance (IR) is considered a primary contributor to elevated CAD risk in diabetic individuals. The triglyceride-glucose (TyG) index serves as a straightforward surrogate marker for insulin resistance. However, few studies have explored their correlations with myocardial infarction and CAD severity. Therefore, our study aimed to investigate the association between the TyG index and the occurrence of myocardial infarction, as well as the severity of coronary artery disease. We conducted a retrospective study involving 3865 consecutive patients who underwent coronary angiography at the First Affiliated Hospital of Zhejiang University, School of Medicine. Of these, 1724 patients were diagnosed with coronary artery disease. Demographic, biochemical, clinical, and angiographic data were gathered. A robust correlation exists between the TyG index and CAD subtypes, suggesting its potential as an independent clinical diagnostic marker. Moreover, the TyG index exhibited a significant positive correlation with disease severity, as assessed by the Gensini score. Elevated TyG index was associated with an increased predisposition to severe CAD, as indicated by the Gensini score, and myocardial infarction, even after adjusting for well-established cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. Methods: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3–5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. Results: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. Conclusions: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Objective: Metabolic syndrome (MetS) and insulin resistance (IR) are associated with diabetes. Insulin therapy in type 1 diabetes (T1DM) may complicate the diagnosis of both these conditions. Therefore, investigation of the diagnostic efficacy of MetS and IR components is important in paediatric population with type 1 diabetes mellitus (T1DM). Methods: SCOPUS, Web of Science, and PubMed were searched for studies that have MetS and IR in paediatric populations with T1DM. We assessed the strength of association for MetS and IR components. A random effect model was used for the meta-analysis and the effect size was reported in terms of Hedge's g. Results: A total 30 studies were identified relevant to our systematic search. Insulin dosage and HbA1c, markers for glycemic condition showed very small effect on MetS with T1DM. In the lipid profile, triglyceride (TG) and low-density lipoprotein (LDL) showed better effect size than high-density lipoprotein (HDL). In case of IR, heterogeneous nature of studies made it difficult to carry out a meta-analysis. A descriptive review of existing and novel markers is thus provided. Conclusion: In children with T1DM, lack of association between markers of glycemic condition suggested that MetS may develop independent of glycemic level. Other than TG and HDL, LDL may be used in the diagnosis of MetS. A universally accepted diagnosis protocol would enhance accuracy and comparability across research and clinical settings, as observed in the descriptive review. [ABSTRACT FROM AUTHOR]

Objective: Limited studies have been conducted on insulin index/load, with inconsistent results regarding the glycemic index/load in relation to cardiometabolic risk factors among people with diabetes. The present study aimed to reveal the association of dietary glycemic index and load and dietary insulin index and load with cardiometabolic risk factors among people with diabetes. Method: This cross-sectional study was performed on 88 adults with diabetes who enrolled in the Cohort Study of Employees of Shiraz University of Medical Sciences. The scores of dietary glycemic index (DGI), dietary glycemic load (DGL), dietary insulin index (DII), and dietary insulin load (DIL) were measured using a 116-item food frequency questionnaire (FFQ). Multivariate linear regressions were used to associate each dietary score with fasting blood glucose (FBG), triglyceride, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and systolic and diastolic blood pressure. Results: DGI was significantly associated with serum FBG (β; 0.24, 95% CI; 0.02, 0.46) and triglyceride (β; 0.53, 95% CI; 0.002, 1.06) levels but not TC, HDL, LDL, or blood pressure after adjusting for age, sex, education, marital status, smoking, body mass index, energy intake, physical activity, having other diseases, and family history of diabetes. Neither DGL, DII, nor DIL was significantly associated with each of the cardiometabolic risk factors after controlling for the confounders. Conclusion: A diet with a higher glycemic index accompanied by a higher serum FBG and triglyceride level. Further studies are needed to determine the association of DGL, DII, and DIL with cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

Objective: The triglyceride glucose (TyG) index and obesity are significantly closely related to the incidence of nonalcoholic fatty liver disease (NAFLD). The study aimed to investigate the relationship among the TyG index and its related parameters [TyG-waist circumference (WC) and TyG-body mass index (BMI)] with NAFLD. Methods: This was a cross-sectional study involving 8401 subjects who underwent a health examination in Karamay, Xinjiang Province, China. TyG, TyG-WC, TyG-BMI were calculated with the established formula. NAFLD was diagnosed and classified by ultrasonography. Results: The prevalence of NAFLD was markedly increased with increasing levels of TyG, TyG-WC and TyG-BMI. Logistic regression analysis suggested that WC, BMI, TyG, TyG-WC and TyG-BMI were independent risk factors for NAFLD. In receiver operating characteristic (ROC) analysis, TyG-BMI showed the largest area under the ROC curve (AUC) for the detection of NAFLD (0.856, 95% confidence interval: 0.848 ~ 0.865), and the results of sex analysis were consistent. TyG-BMI values of 176.69 (sensitivity: 86.9%, specificity: 68.1%), 193.02 (sensitivity: 73.8%, specificity: 73.6%) and 167.73 (sensitivity: 86.3%, specificity: 74.4%) were the optimal cutoff points to predict NAFLD in all participants, males and females, respectively. Conclusions: This study demonstrated that TyG and its related parameters are significantly correlated with NAFLD. TyG-BMI is an effective predictor or clinical marker for identifying NAFLD. [ABSTRACT FROM AUTHOR]

Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes, increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP. [ABSTRACT FROM AUTHOR]

Oral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. Lipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. For this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. We showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Context The relationship between carbohydrate quality intake and metabolic syndrome (MetS) is of growing interest. Objective We aimed to assess the association between the adherence to a dietary carbohydrate quality index (CQI) with the occurrence of MetS in a Spanish cohort of working adults. Methods A cross-sectional study was conducted of 2316 middle-aged men, aged 50.9 (SD 3.9) years, with no previous cardiovascular disease, and pertaining to the Aragon Workers' Health Study (AWHS) cohort. Diet was collected with a 136-item semiquantitative food-frequency questionnaire. The CQI (range 4-15) was based on: dietary fiber intake, a low glycemic index, the ratio of whole grains/total grains, and the ratio of solid carbohydrates/total carbohydrates. The higher the CQI, the healthier the diet. MetS was defined by using the harmonized National Cholesterol Education Programme–Adult Treatment Panel III (NCEP-ATP III) definition. The associations across 3-point categories of the CQI and the presence of MetS were examined using logistic regression. Results An inverse and significant association between the CQI and MetS was found. Fully adjusted odds ratios (ORs) for MetS risk among participants in the 10- to 12-point category (second highest CQI category) was 0.64 (95% CI, 0.45-0.94), and in the 13- to 15-point category (highest category) was 0.52 (95% CI, 0.30-0.88), when compared with the 4- to 6-point category (lowest category). Participants with 10 to 12 and 13 to 15 points on the CQI showed a lower risk of hypertriglyceridemia: OR 0.61 (95% CI, 0.46-0.81), and 0.48 (95% CI, 0.32-0.71) respectively. Conclusion Among middle-aged men, a higher adherence to a high-quality carbohydrate diet is associated with a lower prevalence of MetS. Triglyceridemia is the MetS component that contributed the most to this reduced risk. [ABSTRACT FROM AUTHOR]

Background/Objectives: Reduced serum magnesium (Mg) levels have been associated with obesity, insulin resistance (IR), type 2 diabetes, and metabolic syndrome in adults. However, in the children population, the evidence is still limited. In this cross-sectional study, we aimed to analyze the association of serum Mg levels with the frequency of overweight and obesity and cardiometabolic traits in 189 schoolchildren (91 girls and 98 boys) between 6 and 12 years old from Mexico City. Subjects/Methods: Anthropometrical data were collected and biochemical parameters were measured by enzymatic colorimetric assay. Serum Mg level was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. Results: Serum Mg level was negatively associated with overweight (Odds ratio [OR] = 0.377, 95% confidence interval [CI] 0.231–0.614, p < 0.001) and obesity (OR = 0.345, 95% CI 0.202–0.589, p < 0.001). Serum Mg level resulted negatively associated with body mass index (BMI, β = −1.16 ± 0.26, p < 0.001), BMI z-score (β = −0.48 ± 0.10, p < 0.001) and TyG index (β = −0.04 ± 0.04, p = 0.041). Through a mediation analysis was estimated that BMI z-score accounts for 60.5% of the negative association of serum Mg level with IR (Sobel test: z = 2.761; p = 0.005). Conclusion: Our results evidence that BMI z-score mediate part of the negative association of serum Mg level and IR in Mexican schoolchildren. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder affecting 5–15% of women of reproductive age, characterized by ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. PCOS is associated with metabolic disturbances such as dyslipidemia, insulin resistance (IR), and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Objective: The aim of this study is to apply new anthropometric indices [body adiposity index (BAI), visceral adiposity Index (VAI), lipid accumulation product (LAP), body roundness index (BRI), a body shape index (ABSI)] and new atherogenic indices [Castelli index-I, Castelli index-II, atherogenic risk of plasma (AIP), atherogenic coefficient (AC), lipoprotein combined index (LCI), triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio, metabolic score for insulin resistance (METS-IR), triglyceride glucose (TyG) index, triglyceride glucose-dody mass (TyG-BMI) index, triglyceride glucose-waist circumference (TyG-WC) index] metabolic score of insulin resistance to patients with PCOS. Methods: A retrospective analysis was conducted on 248 women diagnosed with PCOS based on the 2003 Rotterdam criteria. Anthropometric measurements, biochemical parameters, and atherogenic indices were collected from patient records. Statistical analyses were performed using Statistical Package for the Social Sciences software version 28.0. Results: Significant correlations were found between fasting glucose and various anthropometric indices, such as Body mass index (BMI), waist-height ratio (WHtR), and BAI, indicating a link between adiposity and glucose metabolism in PCOS. Atherogenic indices like Castelli's risk indices, AIP, and AC showed positive correlations with glucose and insulin levels, reinforcing their role in assessing cardiovascular risk. Novel indices such as METS-IR and TyG demonstrated strong correlations with both glucose and insulin profiles, highlighting their potential as reliable markers for IR and cardiometabolic risk. Conclusion: The study underscores the importance of using a range of anthropometric and atherogenic indices for comprehensive metabolic assessment in women with PCOS. Indices like METS-IR and TyG offer valuable insights into insulin sensitivity and cardiovascular risk, potentially aiding in better management and prognosis of PCOS. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women. Dyslipidemia is a prevalent metabolic abnormality in individuals with PCOS. Moreover, vitamin D deficiency is widespread across all societal strata, with a particularly heightened prevalence observed in patients afflicted with PCOS. The present study aimed to investigate the level of vitamin D and its correlation with lipid profiles in Iranian women diagnosed with PCOS. Methods: This cross-sectional study was carried out at the PCOS and infertility clinic of Arash Women's Hospital in Tehran. The study encompassed the medical records of PCOS patients who attended the clinic from March 2021 to December 2023. All patients underwent blood tests, which included assessments of fasting blood sugar levels, lipid profiles, and 25-hydroxyvitamin D (25(OH)D) levels. The investigation focused on evaluating the relationship between vitamin D levels and lipid profiles. Statistical analyses, including the chi-square test and Spearman's correlation coefficient, were employed to analyze the data. Results: A total of 1004 women diagnosed with PCOS were included in the study. The age range of the participants was 14 to 46 years. The majority of the participants had a body mass index (BMI) within the normal range (n = 555, 55.3%). The median vitamin D level among the participants was 26.00 (IQR: 19.00–34.00). The relationship between vitamin D levels and lipid profile parameters was assessed, revealing no significant correlation between vitamin D levels and low-density lipoprotein (LDL) (r = 0.021, p = 0.505), high-density lipoprotein (HDL) (r = 0.011, p = 0.719), or triglyceride (TG) (r = -0.026, p = 0.417) levels, both in non-adjusted and age-adjusted analyses. Conclusion: According to the present study, there was no significant correlation between serum 25(OH)D deficiency and elevated TG or LDL levels or decreased HDL levels in PCOS patients. Nevertheless, further prospective studies are needed to determine whether there is a causal relationship between vitamin D deficiency and lipid profile alterations, specifically among PCOS patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Genome-wide association studies (GWAS) of metabolic syndrome (MetS) have predominantly focused on non-Asian populations, with limited representation from East Asian cohorts. Moreover, previous GWAS analyses have primarily emphasized the significance of top single nucleotide polymorphisms (SNPs), poorly explaining other SNP signals in linkage disequilibrium. This study aimed to reveal the interaction between rs651821 and rs2266788, the principal variants of apolipoprotein A5 (APOA5), within the most significant loci identified through GWAS on MetS. Methods: GWAS on MetS and its components was conducted using the data from the Korean Genome and Epidemiology Study (KoGES) city cohort comprising 58,600 individuals with available biochemical, demographic, lifestyle factors, and the most significant APOA5 locus was analyzed further in depth. Results: According to GWAS of MetS and its diagnostic components, a significant association between the APOA5 SNPs rs651821/rs2266788 and MetS/triglycerides/high-density lipoprotein phenotypes was revealed. However, a conditional analysis employing rs651821 unveiled a reversal in the odds ratio for rs2266788. Therefore, rs651821 and rs2266788 emerged as independent and opposing signals in the extended GWAS analysis, i.e., the multilayered effects. Further gene-environment interaction analyses regarding lifestyle factors such as smoking, alcohol consumption, and physical activity underscored these multilayered effects. Conclusion: This study unveils the intricate interplay between rs651821 and rs2266788 derived from MetS GWAS. Removing the influence of lead SNP reveals an independent protective signal associated with rs2266788, suggesting a multilayered effect between these SNPs. These findings underline the need for novel perspectives in future MetS GWAS. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes. Methods: This longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC). Results: Over a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71–2.40) and 2.59 (95% CI: 2.20–3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03). Conclusions: The baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation. Materials and methods: In this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Results: The number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well. Conclusion: The results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS. [ABSTRACT FROM AUTHOR]

Stroke is a severe cerebrovascular disease. This study aimed to determine the association between triglyceride‑glucose (TyG) index and stroke among middle-aged and elderly Chinese. Data was extracted from China Health and Retirement Longitudinal Study survey 2015 and survey 2018. Logistic regression, trend test and subgroup analysis were conducted to assess the association. Possible nonlinear relationships were explored with restricted cubic spline (RCS). Propensity score matching (PSM) was conducted to attenuate the effect of confounding factors. ORs of stroke was positively associated with TyG index. The ORs in RCS analysis also increased with the rising TyG, though p for non-linearity was bigger than 0.05. After PSM, the ORs in the full adjusted models were 1.28 (1.01, 1.62). TyG was suggested as an independent risk factor for stroke in the middle aged and elderly Chinese. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421–0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029–1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920–0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886–0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoporosis is often accompanied by sarcopenia and an increased risk of fractures from falls. Recent studies have indicated a close relationship between lipid metabolism and sarcopenia. Abnormal lipid metabolism may directly impact muscle physiological function and metabolism. OBJECTIVE: To investigate the relationship between lipid metabolism and sarcopenia and evaluate their causal relationship using Mendelian randomization. METHODS: Mendelian randomization was used to explore the causal relationship between low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and muscle mass. Research data from genome-wide association studies were used and a sensitivity analysis was conducted to verify the reliability of the results. Approximate indicators of muscle mass, including trunk lean mass and appendicular lean mass, were used as outcome measures. RESULTS AND CONCLUSION: The study found a negative correlation of low-density lipoprotein cholesterol and triglycerides with muscle mass, while no correlation was observed between high-density lipoprotein cholesterol and muscle mass. The results of the sensitivity analysis indicated a robust causal relationship. Using Mendelian randomization, this study provides evidence of a causal relationship between low-density lipoprotein cholesterol and triglycerides and muscle mass. This finding deepens our understanding of the effects of lipids on sarcopenia and has important clinical implications for the prevention and treatment of sarcopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

The triglyceride glucose (TyG) index, a novel surrogate indicator for insulin resistance (IR), is believed to be associated with various diseases. However, its connection with cognitive decline remains controversy. The PubMed, EMBASE, Cochrane Library, Web of Science, and Medline databases were systematically searched up to October 2023 to assess the association between the TyG index and the risk of cognitive decline. Effect estimates and 95 % confidence intervals (CIs) were calculated using a random-effects model. Our review included 3 cohort studies and 9 case-control/cross-sectional studies with a total of 5,603,350 participants. In comparison to a low TyG index, a higher TyG index was connected to an elevated risk of cognitive decline (RR/HR = 1.14, 95 % CI [1.11, 1.17], P < 0.05; OR = 1.75, 95 % CI [1.34, 2.29], P < 0.05). Furthermore, the dose-response analysis from the case–control/cross–sectional studies revealed a 1.42 times higher risk of cognitive decline per 1 mg/dl increment of the TyG index (OR = 1.42, 95 % CI [1.19, 1.69], P < 0.05). The inclusion of observational studies in the meta-analysis demonstrated a lower hierarchy of evidence compared to randomized controlled trials. Moreover, we incorporated a restricted number of studies and identified significant heterogeneity among them, potentially attributed to the presence of numerous confounding variables. TyG index is related to cognitive decline. In view of some of the limitations of this study, further research will be necessary to confirm this relationship. • Our meta-analysis revealed a positive correlation between overall cognitive decline and TyG index. • The dose-response analysis revealed a 1.42 times higher risk of cognitive decline per 1 mg/dl increment of the TyG index. • Subgroup analysis found that the relationship between TyG index and cognitive decline varies by gender, age, and region. [ABSTRACT FROM AUTHOR]

Background: The Lipid Accumulation Product (LAP) is a measure that indicates excessive fat accumulation in the body. LAP has been the focus of research in epidemiological studies aimed at forecasting chronic and metabolic diseases. This study aimed to evaluate the association between LAP and type 2 diabetes mellitus (T2DM) among adults in western Iran. Methods: The study involved 9,065 adults who participated in the initial phase of the Ravansar non-communicable diseases study (RaNCD) cohort. To investigate the association between LAP and T2DM, multiple logistic regressions were employed. Additionally, the receiver operating characteristic (ROC) curve was used to evaluate LAP's predictive ability concerning T2DM. Results: The participants had an average age of 47.24 ± 8.27 years, comprising 49.30% men and 50.70% women. The mean LAP was 53.10 ± 36.60 for the healthy group and 75.51 ± 51.34 for the diabetic group (P < 0.001). The multiple regression analysis revealed that the odds of T2DM in the second quartile of LAP were 1.69 (95% CI: 1.25, 2.29) times greater than in the first quartile. Furthermore, the odds in the third and fourth quartiles were 2.67 (95% CI: 2.01, 3.55) and 3.73 (95% CI: 2.83, 4.92) times higher, respectively. The ROC analysis for predicting T2DM showed that the LAP index had an area under the curve (AUC) of 0.66 (95% CI: 0.64, 0.68). Conclusion: A strong association was identified between elevated LAP levels and T2DM in the adult population of western Iran. LAP is recommended as a potential tool for screening diabetes susceptibility. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes mellitus (T1DM) is well-known to trigger a disruption of lipid metabolism. This study aimed to compare lipid profile changes in T1DM patients after achieving glucose control and explore the underlying mechanisms. In addition, we seek to identify novel lipid biomarkers associated with T1DM under conditions of glycemic control. Methods: A total of 27 adults with T1DM (age: 34.3 ± 11.2 yrs) who had maintained glucose control for over a year, and 24 healthy controls (age: 35.1 + 5.56 yrs) were recruited. Clinical characteristics of all participants were analyzed and plasma samples were collected for untargeted lipidomic analysis using mass spectrometry. Results: We identified 594 lipid species from 13 major classes. Differential analysis of plasma lipid profiles revealed a general decline in lipid levels in T1DM patients with controlled glycemic levels, including a notable decrease in triglycerides (TAGs) and diglycerides (DAGs). Moreover, these T1DM patients exhibited lower levels of six phosphatidylcholines (PCs) and three phosphatidylethanolamines (PEs). Random forest analysis determined DAG(14:0/20:0) and PC(18:0/20:3) to be the most prominent plasma markers of T1DM under glycemic control (AUC = 0.966). Conclusions: The levels of all metabolites from the 13 lipid classes were changed in T1DM patients under glycemic control, with TAGs, DAGs, PCs, PEs, and FFAs demonstrating the most significant decrease. This research identified DAG(14:0/20:0) and PC(18:0/20:3) as effective plasma biomarkers in T1DM patients with controled glycemic levels. [ABSTRACT FROM AUTHOR]

The objective of this work was to evaluate the properties of beverages formulated with Brazil nuts (Bertholletia excelsa Bonpl) and bocaiuva almonds (Acrocomia aculeata (Jacq.) Lodd. Ex Mart.). Five beverages were developed with Brazil nut, bocaiuva almond, and water (m/m/v), as follows: (i) NB, nut:water, 1:10; (ii) AB, almond:water, 1:10; (iii) NAB1, 1:0.1:10, nut:almond:water; (iv) NAB5, nut:almond:water, 1:0.5:10; and (v) NAB10, nut:almond:water, 1:1:10. The physicochemical, chemical, technological, and microbiological parameters were evaluated. After heat treatment (HT) and enrichment with minerals, the beverages that demonstrated stability in these characteristics were tested in a biological assay. The physical and biochemical parameters of male Wistar rats were evaluated after administering beverages for 28 days. HT decreased the total phenolic content and the antioxidant activity; however, it guaranteed microbiological safety. Mineral supplementation changed the colors and increased the pH values of the beverages. After the beverages were administered, the Wistar rats in the (i) NB group showed decreases in retroperitoneal adipose tissue, total cholesterol, and triglycerides; (ii) those in the AB group exhibited decreased triglycerides contents; and (iii) those in the NAB10-group presented decreased liver weights. The beverages evaluated in this study demonstrate a protective effect against risk factors such as fat accumulation in the liver, retroperitoneal adipose tissue, and hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Context: There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear. Objective: Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD. Methods: The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein–protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments. Results: Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. Discussion and conclusion: The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy. [ABSTRACT FROM AUTHOR]

The objective were to evaluate the effects of supplementation of standardized dry extract of Rosmarinus officinalis (RO) and the application of aesthetic radiofrequency on the oxidative stress markers catalase (CAT), superoxide dismutase (SOD), non-protein thiols (NP-SH), and thiobarbituric acid reactive species (TBARS) and the biochemical markers triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, glutamic-oxaloacetic transaminase (TGO/AST), pyruvic-glutamic transaminase (TGP/ALT), gamma glutamyl transpeptidase (gamma-GT), and creatinine. This study included 32 women received the aesthetic therapy to reduce localized fat. They were divided into the control group (n = 8) receiving placebo capsules and the intervention group (n = 24) subdivided into Group A, B, and C, each with eight members receiving supplementation with 100, 500, and 1000 mg/day of standardized dry extract of RO, respectively. The Universal Trial Number (UTN) – U1111-1274-6255. Supplementation with RO (500 mg/day) demonstrated a reduction in oxidative stress (quantified with through a significant increase in NP-SH and a reduction in SOD and CAT enzymes). The radiofrequency aesthetic treatment did not promote an increase in oxidative stress; however, it caused significant changes in total cholesterol, HDL cholesterol, and creatinine. RO is a plant with antioxidant effects and its oral consumption is safe in selected women subjects in hepatic and renal markers. [ABSTRACT FROM AUTHOR]

Background: Promoting prevalence of metabolic syndrome (MetS) in Rheumatoid arthritis (RA) patients might occur secondary to RA therapy as well as sedentary life style. However, conflicting observations have been reported on the correlation between MetS and RA. This study aimed to determine the frequency of MetS and association of its components in RA. Methods: In this study, 500 RA patients and 500 age- and gender-matched healthy controls were enrolled. MetS was fulfilled through the International Diabetes Federation (IDF) criteria. A multivariate regression model was used to control for variables independently associated with the risk of MetS in RA patients. Results: The prevalence of MetS was 58.8% on IDF criteria in RA patients that was higher than controls (20.4%). Higher incidence of cardiovascular disease (CVD), the familial history of CVD, hypertension, type 2 diabetes mellitus (T2DM), smoking, dyslipidemia, and higher levels of body mass index (BMI), waist circumference (WC), total cholesterol level, fasting blood sugar (FBS), triglyceride (TG) level, low-density lipoprotein (LDL) level, while lower levels of high-density lipoprotein (HDL) were associated with an increased risk of MetS in RA patients. Multivariate regression analysis indicated that age, WC, dyslipidemia, LDL, and DAS28 were independent predictors of MetS in the RA patients. Conclusions: The prevalence of MetS is higher in RA patients. Our findings suggest an association between cardiovascular risk factors and the increased prevalence of MetS in RA patients. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have revealed the role of dietary fatty acids in human health. However, few studies have evaluated dietary fatty acid patterns and their association with metabolic parameters. The current study aimed to explore the association between dietary fatty acid patterns and risk factors for metabolic syndrome (MetS) among overweight and obese adults. Methods: This cross-sectional study involved 340 participants who were overweight or obese. The study included assessments of body composition and anthropometric measurements. Dietary fatty acid consumption was evaluated using a validated Food Frequency Questionnaire (FFQ) containing 168 items. Additionally, biochemical parameters, including serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting serum glucose (FSG), and insulin levels, were measured using enzymatic methods. Fatty acid patterns were determined by principal component analysis (PCA), and the association between these dietary FA patterns and risk factors related to MetS components was assessed using logistic regression. Results: Factor analysis conducted in this study explored three dietary fatty acid patterns: saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), and long-chain combined fatty acids (LC-CFA). Those at the highest tertile of the SFA pattern had lower diastolic blood pressure (DBP) (P = 0.03). Low-density lipoprotein cholesterol (LDL) was lower in the second and third tertiles (P ≤ 0.05). Also, higher fasting blood glucose (FBS) was observed in the second and third tertiles (P < 0.05), and the homeostatic model assessment of insulin resistance (HOMA-IR) was higher in the third tertile (P = 0.049). In the PUFA pattern, FBS was lower in the third tertile (P = 0.03). In the LC-CFA pattern, lower TC was achieved in higher tertiles (P = 0.04). Conclusion: Our findings demonstrated that consuming high and moderate SFA patterns is associated with higher FBS and HOMA-IR. Also, increased consumption of SCFAs is related to lower DPB and LDL. Individuals who consumed more PUFA, especially linoleic acid, had lower FBS. These outcomes might be beneficial in managing MetS and leading to a new field of research. [ABSTRACT FROM AUTHOR]

Aim: Insulin resistance is one of the most common causes of liver fibrosis. Instead of the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) index, which has been used to indicate insulin resistance for many years, Triglyceride-Glucose index (TyG) has recently been used, which is thought to be more predictive. (AST) to Platelet Ratio Index (APRI) and Fibrosis-4 Index (FIB-4) are newly developed markers to indicate liver fibrosis. In this study, we aimed to examine the relationship between TyG and HOMA-IR and APRI and FIB-4. Materials and Methods: 8.618 patients who applied to Turgut Özal Medical Center internal medicine outpatient clinic between March 2019 and March 2024 were retrospectively examined. APRI and FIB-4 levels were compared in patients by grouping them by age and as having/not having insulin resistance according to TyG and HOMA-IR. Results: There was a statistically significant positive correlation between TyG with APRI and FIB4 (ρ=0.041, p<0.001 for APRI and ρ=0.109, p<0.001 for FIB4). There was a significant difference in APRI and FIB-4 in the grouping made according to the presence of insulin resistance. In the grouping made according to glycemic status, FIB-4 was significantly different among all subgroups (p<0.001 for each), while there was no significant difference in APRI. Conclusion: Insulin resistance is one of the conditions that should be closely monitored not only because it predisposes to diabetes but also because it causes dysfunction in liver. Newly diagnosed indexes may be useful to follow-up these patients before any symptoms ocur. Widespread use of these indices especially FIB-4 index which we claim that it is more predictive than others, in clinical practice may be beneficial due to their predictive effects and noninvasiveness. [ABSTRACT FROM AUTHOR]