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Background: It is unknown whether clinical benefit of proprotein convertase subtilisin/kexin type 9 inhibitors is associated with baseline or on-treatment triglyceride concentrations., Objectives: This study sought to examine relations between triglyceride levels and the effect of alirocumab vs placebo on cardiovascular outcomes using prespecified and post hoc analyses of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial., Methods: Patients with recent acute coronary syndrome (ACS) (n = 18,924) and elevated atherogenic lipoproteins despite optimized statin therapy were randomized to alirocumab 75 to 150 mg or matching placebo every 2 weeks subcutaneously. Major adverse cardiovascular events (MACE) were examined in relation to continuous or dichotomous triglyceride concentrations., Results: Median baseline triglyceride concentration was 129 mg/dL. In both treatment groups, a 10-mg/dL higher baseline concentration was associated with an adjusted MACE HR of 1.008 (95% CI: 1.003-1.013; P < 0.005). Baseline triglycerides ≥150 vs <150 mg/dL were associated with a HR of 1.184 (95% CI: 1.080-1.297; P < 0.005). Versus placebo, alirocumab reduced low-density lipoprotein cholesterol from baseline (average, 54.7%) and reduced MACE (HR: 0.85; 95% CI: 0.78-0.93). At month 4, triglyceride levels were reduced from baseline by median 17.7 mg/dL (P < 0.001) and 0.9 mg/dL (P = NS) with alirocumab and placebo, respectively. A 10-mg/dL decline from baseline in triglycerides was associated with lower subsequent risk of MACE with placebo (HR: 0.988; 95% CI: 0.982-0.995; P < 0.005) but not with alirocumab (HR: 0.999; 95% CI: 0.987-1.010; P = 0.82)., Conclusions: Among patients with recent ACS on optimized statin therapy, baseline triglycerides was associated with cardiovascular risk. However, the reduction in triglycerides with alirocumab did not contribute to its clinical benefit. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)., Competing Interests: Funding Support and Author Disclosures This analysis was funded by Regeneron Pharmaceuticals, Inc. The ODYSSEY OUTCOMES trial was funded by Regeneron Pharmaceuticals, Inc, and Sanofi. The trial was designed by an academic steering committee in conjunction with the sponsors. The sponsors were involved in the collection verification, and analysis of the data provided in the manuscript. All authors participated in the interpretation of the data. Dr Zahger has served as national coordinator for the ODYSSEY OUTCOMES trial and the SCORED trial, both funded by Sanofi; and has served as consultant for Bayer, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi. Dr Schwartz has received research support to the University of Colorado from AstraZeneca, Sanofi, Silence Therapeutics, and The Medicines Company; and is a coinventor of pending U.S. patent 62/806,313 (“Methods for Reducing Cardiovascular Risk”) assigned in full to the University of Colorado. Drs Du, Manvelian, Pordy, Fazio, and Geba are all employees of and shareholders in Regeneron Pharmaceuticals, Inc. Dr Szarek has received salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado that receives research grant/consulting funding from Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women’s Hospital, Bristol Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, Everly Health, Faraday, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, MedPace, Medtronic, Moderna, Novate Medical, Novo Nordisk, Pfizer, PhaseBio, PPD Development, Prairie Education and Research, Prothena Biosciences, Regeneron Pharmaceuticals, Inc, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, University of Pittsburgh, Worldwide Clinical Trials, Wraser, and Yale Cardiovascular Research Group; has received fees for performing analyses, steering committee fees, and travel support from Sanofi and Regeneron Pharmaceuticals, Inc; has received consulting fees from CiVi, Lexicon, Amarin, and Esperion Therapeutics; has received Data Safety and Monitoring Board membership fees from Resverlogix and Janssen; and is a member of the Journal of the American College of Cardiology Editorial Board. Dr Bhatt has served on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on the Board of Directors for Angiowave (with stock options), Boston VA Research Institute, Bristol Myers Squibb (with stock), DRS.LINQ (with stock options), High Enroll (with stock), Society of Cardiovascular Patient Care, and TobeSoft; has served as the Inaugural Chair of the American Heart Association Quality Oversight Committee; has served as a consultant for Broadview Ventures and Hims; has served on the Data Monitoring Committee for Acesion Pharma, Assistance Publique–Hôpitaux de Paris, the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), the Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, the Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT trial); has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); has served as the Deputy Editor of Clinical Cardiology; has served as the Chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; holds a patent for sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women's Hospital receives any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Eli Lilly and Company, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron Pharmaceuticals, Inc, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); has served as a site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; is a trustee of the American College of Cardiology; and conducted unfunded research for FlowCo and Takeda. Dr Bittner has received grant support from Sanofi, AstraZeneca, DalCor, Esperion, Bayer, Novartis, and Amgen, all paid direct to her institution; and has received personal fees from Sanofi and Pfizer. Dr Budaj has received personal fees and nonfinancial support from Sanofi, Bristol Myers Squibb/Pfizer, Bayer, and AstraZeneca; and has received personal fee from Novartis, Amgen, and Novo Nordisk. Dr Diaz has received research grants from Sanofi, DalCor Pharmaceuticals, the Population Health Research Institute, Duke Clinical Research Institute, the TIMI group, Amgen, Cirius, the Montreal Health Innovations Coordinating Center, and Lepetit; and has received personal fees, as a member of the Executive Steering Committee, from Amgen and Cirius. Dr Goodman has received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly and Comapny, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, and Sanofi; has received honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly and Company, Esperion Therapeutics, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, JAMP Pharma, Janssen/Johnson & Johnson, Merck, Novartis, Novo Nordisk A/C, Pendopharm, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, Servier, Valeo Pharma, the Canadian Heart Research Centre and MD Primer, the Canadian VIGOUR Centre, the Cleveland Clinic Coordinating Centre for Clinical Research, the Duke Clinical Research Institute, the New York University Clinical Coordinating Centre, the PERFUSE Research Institute, and the TIMI Study Group (Brigham Health); and has served as a consultant or on the advisory board (or both) for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Janssen/Johnson & Johnson, Merck, Novartis, Pendopharm, Pfizer, Regeneron Pharmaceuticals, Inc, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma. Dr Jukema has received research grants from the Netherlands Heart Foundation, the Interuniversity Cardiology Institute of the Netherlands, and the European Commission Seventh Framework Programme; and has received research support from Amgen, Astellas, AstraZeneca, Daiichi-Sankyo, Eli Lilly and Company, Merck-Schering-Plough, Pfizer, Roche, and Sanofi. Dr Harrington has received research grants (all data safety and monitoring board related) from AstraZeneca, Janssen, and Bristol Myers Squibb; has served on the advisory board for Gilead (uncompensated) and WebMD; and has served on the board of directors (unpaid) for the American Heart Association and Stanford HealthCare. Dr Moriarty has received research grants to his institution for the participation in the ODYSSEY OUTCOMES trial; has received financial fees for serving as a medical monitor for the trial and associated support for travel related to trial meetings from Sanofi; has received consulting and speaking fees from Regeneron Pharmaceuticals, Inc, and Amgen; has received consulting fees from Esperion, Kaneka, and Stage II innovations; has received speaker fees from Amarin; has received advisor fees from Novartis for serving on their advisory committee; and has received research grants to his institution from Ionis, FH Foundation, GB Life Sciences, Aegerion, Amgen, Kowa, Novartis, and Regeneron Pharmaceuticals, Inc. Dr Scemama is an employee of Sanofi and may hold shares and/or stock options in the company. Dr White has received grant support paid to his institution for serving on a Steering Committee for the ODYSSEY OUTCOMES trial from Sanofi and Regeneron Pharmaceuticals, Inc, for the ACCELERATE study from Eli Lilly and Company, for the STRENGTH trial from Omthera Pharmaceuticals, for the CAMELLIA-TIMI study from Eisai, for the HEART-FID study from American Regent, and for the ISCHEMIA Trial and the MINT Trial from the National Institutes of Health; has received grants to his institution and personal fees as Steering Committee member for the dal-GenE study from DalCor Pharma UK Inc, for the AEGIS-II study from CSL Behring, for the SCORED trial and the SOLOIST-WHF trial from Sanofi Australia Pty Ltd, and for the CLEAR Outcomes Study from Esperion Therapeutics Inc; and has served on the advisory board for CSL Behring and Genentech (an affiliate of F. Hoffmann-La Roche Ltd, “Roche”; Lytics Post-PCI Advisory Board at European Society of Cardiology). Dr Zeiher has received fees for serving on a steering committee for the ODYSSEY OUTCOMES trial from Sanofi; and has received advisory board and speaker fees from Sanofi, Amgen, Boehringer Ingelheim, Bayer, Novartis, Pfizer, AstraZeneca, and Vifor. Dr Steg has received grants and nonfinancial support (co-Chair of the ODYSSEY OUTCOMES trial; as such, he received no personal fees, but his institution has received funding for the time he has devoted to trial coordination, and he has received support for travel related to trial meetings) from Sanofi; has received research grants and personal fees from Bayer (Steering Committee MARINER, grant for epidemiological study), Merck (speaker fees, grant for epidemiological studies), Sanofi (co-Chair of the ODYSSEY OUTCOMES trial; co-Chair of the SCORED trial; consulting; speaking), Servier (Chair of the CLARIFY registry; grant for epidemiological research), and Amarin (executive steering committee for the REDUCE-IT trial [Disease Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial]; consulting); has received personal fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Idorsia, MyoKardia, Novo Nordisk, Novartis, Regeneron Pharmaceuticals, Inc, and AstraZeneca; and has a European application number/patent number, issued on October 26, 2016 (no. 15712241.7), for a method for reducing cardiovascular risk, with all royalties assigned to Sanofi. Dr Kiss has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF., Methods: Summary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study's focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods., Results: There was no significant effect of blood lipid traits on IPF risk (all P＞0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05-7.12, P = 0.039), 1.36 (1.02-1.82, P = 0.037), 1.66 (1.12-2.45, P = 0.011), 1.68 (1.14-2.48, P = 0.009), and 1.42 (1.20-1.67, P = 3.17×10 -5 ), respectively. The SMR method identified a significant association between PCSK9 gene expression in whole blood and reduced IPF risk (OR = 0.71, 95% CI: 0.50-0.99, P = 0.043). Sensitivity analyses showed no evidence of bias., Conclusions: Serum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation., (© 2024. The Author(s).)

It is internationally recognized to use clinical decision limits (CDL) when interpreting the lipid levels in both adults and children, even though the evidence for children is scarce. The purpose of this study is to describe how lipid levels progress in healthy Danish children ages 5 to 17 years. This study is based on the Childhood Health, Activity, and Motor Performance School Study Denmark (CHAMPS-study DK) consisting of 1456 observations of schoolchildren aged 5 to 17 years. Participants have been tested for blood levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and remnant cholesterol levels are calculated. Finally, sex-specific percentile reference curves are presented. Percentile reference curves stratified by sex were generated for all cholesterols and showed that the total cholesterol level peaks at 4.32 mmol/l in 10-year-old boys and 4.46 mmol/l in nine-year-old girls. HDL levels in boys peak at 1.72 mmol/l in nine-year-old boys. HDL levels in girls and LDL levels in both sexes are nearly constant. Triglycerides kept rising to the age of 17 years in both sexes and remnant cholesterol decreased from age 5 to 17 years in both sexes. BMI z-score adjustment revealed no significant association with total cholesterol in both sexes but a significant association between HDL, LDL, triglycerides, and remnant cholesterol. This study is the first to generate percentile reference curves for blood levels of total cholesterol, LDL, HDL, triglycerides, and remnant cholesterol in a cohort of healthy Danish children aged 5 to 17 years.

Background and Aims: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial., Methods: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT., Results: In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial., Conclusions: Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BGN reports consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, Silence Therapeutics, Abbott, Mankind, Lilly, and Arrowhead. TD reports a consultancy by Novo Nordisk. AL reports a talk sponsored by Amarin and a consultancy by Novartis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women., Methods: The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders., Results: The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) ( p  = 0.002 and p  < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol ( p  = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) ( p  = 0.024, p  = 0.003 and p  < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C ( p  = 0.024)., Conclusions: In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Hypertriglyceridemia (HTG) is a common cardiovascular risk factor characterized by elevated triglyceride (TG) levels. Researchers have assessed the genetic factors that influence HTG in studies focused predominantly on individuals of European ancestry. However, relatively little is known about the contribution of genetic variation of HTG in people of African ancestry (AA), potentially constraining research and treatment opportunities. Our objective was to characterize genetic profiles among individuals of AA with mild-to-moderate HTG and severe HTG versus those with normal TGs by leveraging whole-genome sequencing data and longitudinal electronic health records available in the All of Us program. We compared the enrichment of functional variants within five canonical TG metabolism genes, an AA-specific polygenic risk score for TGs, and frequencies of 145 known potentially causal TG variants between HTG patients and normal TG among a cohort of AA patients (N = 15,373). Those with mild-to-moderate HTG (N = 342) and severe HTG (N ≤ 20) were more likely to carry APOA5 p.S19W (odds ratio = 1.94, 95% confidence interval = [1.48-2.54], P = 1.63 × 10 -6 and OR = 3.65, 95% confidence interval: [1.22-10.93], P = 0.02, respectively) than those with normal TG. They were also more likely to have an elevated (top 10%) polygenic risk score, elevated carriage of potentially causal variant alleles, and carry any genetic risk factor. Alternative definitions of HTG yielded comparable results. In conclusion, individuals of AA with HTG were enriched for genetic risk factors compared to individuals with normal TGs., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM., Methods: Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment., Results: Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI)., Conclusion: The study demonstrates a significant causal relationship between apoA-I and GDM risk., (© 2024. The Author(s).)

Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apolipoprotein B-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglyceride (TG) and not phospholipid (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different β-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in β2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in β1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, whereas negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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]

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.

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.

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: 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]

Fibroblast growth factor 21 (FGF-21) has been suggested as a potential therapeutic target for insulin resistance in health-related metabolic disorders such as type 2 diabetes. Despite the metabolic effects of resistance (RT) and aerobic training (AT) on diabetes symptoms, uncertainty exists regarding the superiority of effects manifested through these training approaches on FGF-21 and biochemical and physiological variables associated with metabolic disorders in men diagnosed with type 2 diabetes. This study aimed to investigate the impact of a 12-week RT and AT on FGF-21 levels and symptoms associated with metabolic disorders in male individuals diagnosed with type 2 diabetes. Thirty-six sedentary obese diabetic men (40 to 45 years old) were matched based on the level of FGF-1. They and were randomly divided into two training groups (RT, n = 12 and AT, n = 12) performing three days per week of moderate-intensity RT or AT for 12 weeks and an inactive control group (n = 12). Both training interventions significantly improved FGF-21, glucose metabolism, lipid profile, hormonal changes, strength, and aerobic capacity. Subgroup analysis revealed that RT had greater adaptive responses (p < 0.01) in fasting blood sugar (ES = -0.52), HOMA-IR (ES = -0.87), testosterone (ES = 0.52), cortisol (ES = -0.82), FGF-21 (ES = 0.61), and maximal strength (ES = 1.19) compared to AT. Conversely, AT showed greater changes (p < 0.01) in cholesterol (ES = -0.28), triglyceride (ES = -0.64), HDL (ES = 0.46), LDL (ES = -0.73), and aerobic capacity (ES = 1.18) compared to RT. Overall, both RT and AT interventions yielded significant moderate to large ES in FGF-21 levels and enhanced the management of biochemical variables. RT is an effective method for controlling FGF-21 levels and glucose balance, as well as for inducing hormonal changes. On the other hand, AT is more suitable for improving lipid profiles in overweight men with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Concurrent Exercise Training (CET) is defined as an exercise training mode in which aerobic and resistance exercises are performed in the same session. Objectives: The effects of CET in type 2 diabetes mellitus (T2DM) are inconclusive. Therefore, the objective of the present systematic review with a meta-analysis is to evaluate the effects of CET on metabolic markers, body composition, lipid profile, inflammation, and cardiorespiratory fitness (CRF) in people with T2DM. Methods: Five electronic databases were searched from inception up to January 2023. The eligibility criteria included prospective studies that had T2DM participants aged between 35 and 65 years who performed CET at least 2 times/week for a minimum duration of 8 weeks with a control group. Results: Seven studies were identified for qualitative review. Sufficient data were not available for one study, therefore, meta-analysis was performed in six studies. A significant effect was observed in glucose level (p <.01); glycated hemoglobin (p =.02); Homeostatic Model Assessment for Insulin Resistance (p =.02); body mass index (p =.02); %body fat (p <.01); %fat-free mass (p <.01); waist circumference (p =.03); triglyceride (p <.01); peak oxygen uptake (p <.01); and tumor necrotic factor -α (p <.01). Conclusions: The CET is effective in improving metabolic markers, body composition, lipid profile, inflammation, and CRF in people with T2DM and can be included in the management of T2DM. The overall evidence for this conclusion may be influenced by bias in included studies. [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]

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]

The purpose of this study was to investigate the effects of contamination of venous blood with a lipid-containing solution on parameters measured by a modern blood gas analyzer. We collected venous blood from 17 healthcare workers (46 ± 11 years; 53 % women) into three blood gas syringes containing 0 , 5 and 10 % lipid-containing solution. Blood gas analysis was performed within 15 min from sample collection on GEM Premier 5000, while triglycerides and serum indices were assays on Roche COBAS C702. Triglycerides concentration increased from 1.0 ± 0.3 mmol/L in the uncontaminated blood gas syringe, to 39.4 ± 7.8 and 65.3 ± 14.4 mmol/L (both p<0.001) in syringes with 5 and 10 % final lipid contamination. The lipemic and hemolysis indices increased accordingly. Statistically significant variation was noted for all analytes except hematocrit and COHb in the syringe with 5 % lipids, while only COHb did not vary in the syringe with 10 % lipids. Significant increases were observed from 5 % lipid contamination for pO2, SO2 and lactate, while the values of pH, pCO2, sodium, potassium, chloride, ionized calcium, glucose, hematocrit (10 % contamination), hemoglobin and MetHB decreased. All these changes except lactate and CoHb exceeded their relative performance specifications. Artifactual hyperlipidemia caused by contamination with exogenous lipids can have a clinically significant impact on blood gas analysis. Manufacturers of blood gas analyzers must be persuaded to develop new instruments equipped with serum indices. [ABSTRACT FROM AUTHOR]

To investigate the role of body mass index (BMI), serum lipid profile molecules and their derivative indexes in colorectal polyps. A total of 352 individuals who underwent colonoscopy at our center were included in this retrospective analysis. Of these, 247 patients without evident abnormalities (control group), while 105 patients diagnosed with colorectal polyps (patient group). Serum lipid profile molecules and their derivative indexes were then compared between the two groups. The patient group exhibited significantly higher levels of total cholesterol (TC) and apolipoprotein B (ApoB) compared to the control group (p<0.05). In males, the patient group displayed elevated levels of ApoB and ApoB/ApoA1 ratio compared to the control group (p<0.05). Additionally, the triglycerides (TG) and TG/high-density lipoprotein-cholesterol (HDL-C) ratios were significantly higher in the multiple polyps group than in the single polyp group (p<0.05). Furthermore, the HDL-C and HDL-C/ApoA1 ratio levels were higher in the adenomatous polyp group when compared to the non-adenomatous polyp group (p<0.05). Multiple logistic regression analysis indicated that total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), TC/HDL-C ratio, TG/HDL-C ratio and LDL-C/HDL-C ratio were risk factors for the occurrence of colorectal polyps (p<0.05). ROC curve analyses revealed that TC, ApoB, and ApoB/ApoA1 ratio were associated with colorectal polyps. No significant difference in BMI between the two groups (p>0.05). The incidence and progression of colorectal polyps are linked to serum lipid molecules and their derivative indexes. Dyslipidemia may increase the risk of colorectal polyps, potentially leading to colorectal cancer (CRC). [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]

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: 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]

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]

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid–lipoprotein profile, inflammation, and glucose–insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 < p < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11–1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: −0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: −0.42 to −0.84 (small to large effects), p ˂ 0.05). Glucose–insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype. [ABSTRACT FROM AUTHOR]

Background: Obesity and its associated complications raise significant public concern, revealing gender disparities in the susceptibility to metabolic disorders, with females often displaying greater resistance to obesity-related metabolic disorder than males. Sestrin2 is a crucial protein involved in metabolism and energy balance. This study seeks to explore whether Sesn2 knockout (KO) exacerbates high-fat diet (HFD) induced obesity in female mice. Methods: Female mice with wild-type (WT) and Sesn2 KO were subjected to a 12-week regimen of normal diet or HFD. Using a Body Composition Analyzer, body composition was gauged. Biochemical assays encompassed glucose, lipid, and liver function measurements, alongside 24-hour urine albumin excretion. Echocardiographic evaluation assessed cardiac function. Histopathological analysis of key metabolic tissues (liver, kidney, and heart tissues) were conducted. Western blotting or qRT-PCR evaluated key proteins and genes linked to inflammation, mitochondrial, and lipid metabolism in adipose tissues. Results: In comparison to mice fed a regular diet, those on a HFD exhibited significant increases in body weight and fat mass. Notably, Sesn2 KO further aggravated obesity, showcasing the most pronounced metabolic anomalies: elevated body weight, fat mass, impaired glucose tolerance, and insulin sensitivity, alongside heightened levels of free fatty acids and triglycerides. Additionally, KO-HFD mice displayed exacerbated multi-tissue impairments, including elevated hepatic enzymes, increased urinary albumin excretion, compromised cardiac function, and accumulation of lipids in the liver, kidney, and heart. Moreover, adipose tissue showcased altered lipid dynamics and function, characterized by enhanced triglyceride breakdown and modified adipokine levels. Browning was diminished, along with decreased Pgc1α and Sirt1 in KO-HFD mice. Conclusion: Sesn2 KO exacerbates HFD-induced obesity and metabolic disorders in female mice. These findings underscore Sestrin2's novel role as a regulator of obesity in female mice. [ABSTRACT FROM AUTHOR]

Context Cottonseed oil (CSO) is higher in polyunsaturated fatty acids (PUFA) and saturated fatty acids (SFAs) than many liquid plant oils. Objectives To conduct a systematic review of randomized controlled trials (RCTs) examining effects of CSO on markers of lipid metabolism and evaluate lipid and lipoprotein effects of incorporating CSO into a healthy dietary pattern using regression equations. Data Sources A systematic search was conducted for RCTs comparing CSO with a non-CSO comparator in any population. Data Analyses The Katan regression equation was used to predict lipid/lipoprotein changes when incorporating CSO into a US-style healthy eating pattern at 25 to 100% of the total oil allowance (ie, 27 g/2000 kcal) compared with average American intake (NHANES 2017 to 2020 pre-COVID pandemic). Results In total, 3 eligible publications (n = 2 trials), with 58 participants that provided 44% and 30% of total energy as CSO, were included. Fasting low-density lipoprotein cholesterol (LDL-C; ≈ –7.7 mg/dL) and triglycerides (≈ –7.5 mg/dL) were lower after 5 days of a CSO-enriched diet vs olive oil (OO). In a 56-day trial, CSO lowered total cholesterol (TC; ≈ –14.8 mg/dL), LDL-C (≈ –14.0 mg/dL), and non–high-density lipoprotein cholesterol (≈ –14.2 mg/dL) vs OO. Postprandially, angiopoietin-like protein-3, -4, and -8 concentrations decreased with CSO and increased with OO intake. Compared with average American intake, a healthy eating pattern with 27 g of CSO was estimated to lower TC (–8.1 mg/dL) and LDL-C (–7.3 mg/dL) levels, with minimal reduction in high-density lipoprotein cholesterol (–1.1 mg/dL). Compared with the healthy eating pattern, incorporating 27 g of CSO was predicted to increase TC and LDL-C levels by 2.4 mg/dL. Conclusion Limited high-quality research suggests CSO may improve lipid/lipoprotein levels compared with OO. Cholesterol predictive equations suggest CSO can be incorporated into a healthy dietary pattern without significantly affecting lipids/lipoproteins. [ABSTRACT FROM AUTHOR]

The central nervous system continuously detects circulating concentrations of lipids such as fatty acids and troglycerides. Once information has been detected, the central nervous system can in turn participate in the control of energy balance and blood sugar levels and in particular regulate the secretion and action of insulin. Neurons capable of detecting circulating lipid variations are located in the hypothalamus and in other regions such as the nucleus accumbens, the striatum or the hippocampus. An excess of lipids will have deleterious effects and may induce central lipotoxicity, in particular following local production of ceramides and the appearance of neuroinflammation which may lead to metabolic diseases such as obesity and type 2 diabetes. • Both specialized neurons and non-neuronal cells can sense circulating lipids. • lipoprotein lipase in neurons and astrocytes sense triglycerides-enriched lipoproteins. • Ceramides can induce brain lipotoxicity associated with neuroinflammation. [ABSTRACT FROM AUTHOR]

Emerging scientific studies have supported the hypothesis that exposure to environmental chemicals increases the incidence of diverse human metabolic disorders. Therefore, this study aimed to evaluate the association between fluoride exposure and metabolic syndrome (MetS) prevalence in people from the Central Region of Mexico. This research included 575 adult individuals. Urinary fluoride concentrations were determined using a potentiometric method. Anthropometric measurements and blood pressure were also acquired. Serum fasting glucose and lipid levels were quantified. For the MetS screening, we used the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The mean urinary fluoride levels were 3.50 ± 2.50 mg/L. The prevalence of MetS was approximately 27 and 25% according to NCEP ATP III and IDF criteria, respectively. A multivariate logistic regression analysis showed significant associations (p < 0.05) between urinary fluoride concentrations and MetS occurrence using NCEP ATP III criteria (OR = 1.60; 95% CI 1.05–2.10) and IDF criteria (OR = 1.35; 95% CI 0.95–1.45). These findings emphasize the need to discover the underlying mechanisms that fluoride exposure has on MetS pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in adolescents with obesity. Nonetheless, the guidelines for screening and managing this disease are contradictory. The purpose of this study is to non-invasively assess the prevalence, patient characteristics, and potential associated factors of MASLD in this demographic. Methods: This study used baseline data from an RCT in adolescents eligible for bariatric surgery. MASLD was determined by measuring the hepatorenal index (HRI) with ultrasonography, blood liver tests, and the fatty liver index (FLI). Results: A total of 56 adolescents enrolled in the analyses; the majority were female n = 44 (79%); the mean age was 15.75 (±1.01) years; the average body mass index (BMI) was 44.08 (±5.16) kg/m2. In 35 (62.5%) of the patients, the HRI was abnormal. This group had a higher waist/hip ratio, elevated liver biochemistry, and significantly lower leptin levels (mean difference = −46.35, 95% CI −76.72, −15.99) compared to the group with a normal HRI. In 32 (55.2%) of the patients, ALT levels were elevated and the FLI was abnormal in all (100%) participants. Linear regression analysis indicated associations between the HRI and typical anthropometric and metabolic measurements; and an inverse association between HRI and leptin B = −0.003 (95% CI −0.005, −0.00), independently of sex- and age-adjusted BMI. Conclusions: MASLD is highly prevalent in adolescents with severe obesity. However, the prevalence strongly depends on which tool is used, namely the HRI (62.5%), alanine transaminase levels (55.2%), and FLI (100%). Our findings suggest that leptin may be a valuable biomarker in supporting the diagnosis of MASLD. [ABSTRACT FROM AUTHOR]

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to evaluate the impact of VLCKD on cardiovascular risk factors in patients with T2DM. Methods: Until March 2024, extensive searches were conducted on PubMed, Scopus, Web of Science, Embase, and other relevant databases. The purpose was to identify clinical trials examining the impact of VLCKD on glycemic control, lipid profile, and blood pressure. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method was used to assess the evidence's degree of certainty. Results: Our initial search found a total of 2568 records and finally 29 trials were included in final analysis. Our results showed that adherence from VLCKD led to significant reduction in fasting blood sugar (WMD= -11.68 mg/dl; 95% CI: -18.79, -4.56; P = 0.001), HbA1c (WMD= -0.29; 95% CI: -0.44, -0.14; P < 0.001), HOMA-IR(WMD= -0.71; 95% CI: -1.14, -0.29; P = 0.001), insulin (WMD= -1.45; 95% CI: -2.54, -0.36; P = 0.009), triglyceride (WMD= -17.95; 95% CI: -26.82, -9.07; P < 0.001), systolic blood pressure (WMD= -2.85, 95% CI: -4.99, -0.71; P = 0.009) and diastolic blood pressure (WMD= -1.40; 95% CI: -2.66, -0.13; P = 0.03). We also found a significant increase in high-density lipoprotein (HDL) level after adherence from VLCKD diet (WMD = 3.93, 95% CI: 2.03, 5.84; P = 0.000). We couldn't find any significant differences between groups in term of LDL and total cholesterol levels. Conclusion: People following a VLCKD experience a more significant improvement in cardiovascular risk factors when compared to individuals on control diets. [ABSTRACT FROM AUTHOR]

Objective: Betatrophin is a hepatokine that modulates hepatic glucose and lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis. Therefore, this study aimed to investigate the relationship between NAFLD and betatrophin levels in hypogonadal males. Methods: The study included 56 newly diagnosed hypogonadal males aged 18-60 and 60 eugonadal males of similar age and body mass index. All participants were assessed for anthropometric and metabolic parameters, liver function tests, and betatrophin levels. Transient elastography was used to evaluate liver steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)]. Accordingly, hypogonadal and control groups were divided into NAFLD (n = 64) and non-NAFLD (n = 52). Results: Controlled attenuation parameter, LSM, waist circumference (WC), triglycerides (TG), IR index homeostasis model assessment (HOMA-IR), and betatrophin were significantly higher in the hypogonadal group than controls. Hepatic steatosis and fibrosis (67.9%-43.3%) were higher in hypogonadal males. Triglycerides, HOMA-IR, and betatrophin were higher, and total testosterone was significantly lower in the NAFLD group. Serum betatrophin was also significantly higher in patients with fibrosis than without. There was a significant positive correlation between WC, TG, HOMA-IR, betatrophin, and LSM and CAP. The predictive factors were TG (ß = 0.329, P < .001), betatrophin (ß = 0.221, P = .029), HOMA-IR (ß = 0.213, P = .019) for CAP, and betatrophin for LSM (ß = 0.466, P < .001). Conclusion: Non-alcoholic fatty liver disease is more common in hypogonadal males than in eugonadal males. Betatrophin is an independent risk factor for developing and progressing NAFLD. However, more research is needed to explain the causal relationship between betatrophin and NAFLD. [ABSTRACT FROM AUTHOR]

Background: Most studies have focused on comparing blood lipid biomarkers between Parkinson's disease (PD) and normal controls (NC). However, further research is necessary to explore the impact of blood lipid levels on motor and cognitive function, as well as the progression of motor dysfunction and cognitive decline over time. Thus, the aim of this study is to investigate the relationship between blood lipid biomarkers and these indicators in individuals with PD. Methods: The cohort study enrolled 157 PD patients and 146 NC from the Tianjin Huanhu Hospital from September 2017 to September 2019. Serum lipid fractions were detected in fasting serum samples. PD patients were followed up at 2 ± 0.6 years for clinical assessment. Results: PD patients exhibited lower serum triglyceride (TG) levels as compared to NC (P = 0.008). PD male patients exhibited lower serum lipoprotein cholesterol(LDL‐C) and total cholesterol (TC) levels than female patients (LDL‐C: P = 0.034; TC: P = 0.019). Serum TG levels correlated significantly with Unified PD Rating Scale III, Hoehn and Yahr stage and Montreal Cognitive Assessment scores in PD patients. Additionally, serum TG levels were associated with follow‐up motor function decline and cognitive decline in adjusted regression models in PD patients. Conclusions: To summarise, the study findings suggest that decreased serum TG levels are significantly associated with greater motor dysfunction, cognitive dysfunction and the greater deterioration of the two indicators. [ABSTRACT FROM AUTHOR]

Sugar-sweetened beverage (SSB) and fruit juice (FJ) consumption may promote lipid abnormalities in childhood. We examined the association between SSB/FJ intake and lipid levels using electronic health record data for 2816 adolescents. Multivariable logistic regression models treated clinical cutpoints for abnormal lipid levels (triglycerides [TG], high-density lipoprotein (HDL), low-density lipoprotein [LDL], and total cholesterol) as dependent variables. In models not adjusted for adiposity, elevated SSB and FJ consumption was associated with increased odds of having abnormally high TG (SSB: odds ratio [OR] = 1.28 (95% confidence interval [CI] = [1.07-1.52], P =.007); FJ: 1.35 ([1.09-1.69], P =.007)) and abnormally low HDL (SSB: 1.47 ([1.17-1.86], P =.001); FJ: 1.35 ([1.02-1.78], P =.03)). Adjusting for adiposity, a likely mediator of the relationship, attenuated these associations. These findings support the need for identifying unhealthy beverage consumption habits during childhood health care visits as a modifiable behavior associated with cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Objective Low-density lipoprotein cholesterol (LDL-C) has been commonly calculated by equations, but their performance has not been entirely satisfactory. This study aimed to develop a more accurate LDL-C prediction model using machine learning methods. Methods The study involved predicting directly measured LDL-C, using individual characteristics, lipid profiles, and other laboratory results as predictors. The models applied to predict LDL-C values were multiple regression, penalized regression, random forest, and XGBoost. Additionally, a novel 2-step prediction model was developed and introduced. The machine learning methods were evaluated against the Friedewald, Martin, and Sampson equations. Results The Friedewald, Martin, and Sampson equations had root mean squared error (RMSE) values of 12.112, 8.084, and 8.492, respectively, whereas the 2-step prediction model showed the highest accuracy, with an RMSE of 7.015. The LDL-C levels were also classified as a categorical variable according to the diagnostic criteria of the dyslipidemia treatment guideline, and concordance rates were calculated between the predictive values obtained from each method and the directly measured ones. The 2-step prediction model had the highest concordance rate (85.1%). Conclusion The machine learning method can calculate LDL-C more accurately than existing equations. The proposed 2-step prediction model, in particular, outperformed the other machine learning methods. [ABSTRACT FROM AUTHOR]

• Early ovarian cessation even in young women play a role in development of unfavorably altered lipid profile. • Women with newly diagnosed POI exhibited adverse lipid profile along with higher fasting glucose level in contrary to age-matched healthy controls. • Women with non-idiopathic POI present unfavorably altered lipid profile when compared to women with unknown cause of POI. Hypoestrogenism related to the cessation of ovarian function increases the risk of metabolic disorders in postmenopausal women. Women with primary ovarian insufficiency (POI) are exposed to longer period of estrogen deficiency together with a subsequently higher risk of long-term comorbidities. To compare metabolic along with hormonal status among newly diagnosed women with POI with pre- and postmenopausal women. To investigate the impact of POI etiology on both metabolic and hormonal profiles. A case-control study with women assigned to one of the groups: 1) POI (n = 216), 2) age-matched premenopausal (n = 216), 3) postmenopausal (n = 227). Lipid profile, fasting glucose and insulin levels together with insulin resistance were determined among all participants. POI women exhibited increased both total cholesterol (TC, p = 0.04) and low-density lipoprotein cholesterol (LDL-C, p < 0.01) compared to the premenopausal women and higher triglycerides (TG, p < 0.001) than postmenopausal women. POI group showed higher fasting glucose level (p = 0.04) differently to premenopausal women. The idiopathic POI group showed both lower sex hormone binding globulin (p = 0.02) and dehydroepiandrosterone sulfate (p = 0.04) along with reduced TC (p = 0.03) and TG (p = 0.01) together with increased high-density lipoprotein cholesterol (p = 0.04) levels than non-idiopathic POI women. Women with newly diagnosed POI exhibited less favorable lipid profile than pre- or postmenopausal women. The association of negatively changed lipid profile in POI women is mostly mediated by women with unknown cause of premature ovarian cessation. [ABSTRACT FROM AUTHOR]

Background: The prevalence of pulmonary hypertension (PH) is reported between 17% and 56% in hemodialysis patients. The pathogenesis of PH in hemodialysis patients is still unclear. Malnutrition may be associated with impaired pulmonary function in hemodialysis patients. Objectives: The present study aimed to investigate the association between PH and nutritional and biochemical markers in hemodialysis patients. Methods: In this cross-sectional study, 80 patients undergoing hemodialysis at the Kowsar Medical Center, Semnan, Iran, from 1 March 2016 to 31 August 2016 were enrolled by complete enumeration. Pulmonary artery pressure was determined by echocardiography between hemodialysis sessions. Arm circumference, triceps fat mass, and body mass index (BMI) were determined. Other laboratory tests included transferrin, serum albumin, cholesterol, triglyceride, and hemoglobin. The source of receiving protein was recorded in a questionnaire. The data were analyzed by the chi-square test and logistic regression analysis at a significance level of less than 0.05. Results: Pulmonary hypertension ( > 25 mmHg) was found in 32 (40%) of the 80 patients studied. The mean of pulmonary pressure in patients with PH was 34.66 ± 5.6 mmHg compared to 16.85 ± 3.7 mmHg in patients without PH. Age, gender, arm circumference, frequency of dialysis per year, and serum levels of albumin, transferrin, triglyceride, and total cholesterol were not significantly different between patients with and without PH. There was a significant difference in the mean hemoglobin level between patients with and without PH (P = 0.003). The likelihood of developing PH was reduced by 0.3 in those with hemoglobin ≥ 11 g/dL compared to patients with hemoglobin levels below 11 g/dL (OR = 0.400, P = 0.003). The likelihood of developing PH in patients with albumin ≥ 3.8 g/L decreased by 0.126 compared to those with albumin less than 3.8 (OR = 0.126, P = 0.003). Conclusions: The results of our study indicated a higher incidence of PH in patients with lower levels of hemoglobin and albumin. So, patients undergoing hemodialysis are recommended to be regularly screened for these two variables. [ABSTRACT FROM AUTHOR]

With increasing age, dyslipidemia becomes a common health problem in the middle-aged and elderly population, posing a significant risk of cardiovascular disease. Aerobic exercise, as a non-pharmacological intervention, is considered to be effective in improving blood lipid levels, but the extent to which different types of aerobic exercise affect blood lipids is not clear. This study aims to investigate the effects of 12 different aerobic exercises on total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in middle-aged and elderly people aged 45 years and over through systematic review and Bayesian network Meta-analysis of randomized controlled trials. We systematically searched relevant databases and included eligible randomized controlled trials. Bayesian network meta-analysis was used to compare the effects of 12 types of aerobic exercise on lipid levels. A total of 487 randomized controlled trials involving middle-aged and elderly people over 45 years old were included. The results of the network meta-analysis showed that all types of aerobic exercise could reduce blood lipid levels compared with no intervention in middle-aged and elderly people. In terms of total cholesterol, triglyceride, and low-density lipoprotein cholesterol, swimming had the most significant effect. For HDL cholesterol, dance showed a better effect. Studies have shown that swimming and dancing have a positive effect on improving blood lipid levels in middle-aged and elderly people. It is recommended to choose the appropriate type of exercise according to personal preference and physical condition. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a major health hazard today. Clinically significant macular oedema (CSME) is the most frequent cause of decreased vision in diabetic patients. The aim of our study was to determine whether CSME in subjects with type 2 DM is associated with lipid profile abnormalities and to compare them with lipid profiles of type 2 diabetics without CSME. Method: This was a cross-sectional case-control study. Hundred consecutive type 2 diabetic patients, 50 patients with and 50 without CSME, who attended the Retina outpatient clinic of a tertiary eye hospital over a one-year period, were included. Determination of the presence of CSME and staging of diabetic retinopathy was done according to modified Early Treatment Diabetic Retinopathy Study guidelines, by a single investigator using slit-lamp biomicroscopy. After obtaining informed consent, blood was drawn from the subjects after overnight fasting. Investigations done were lipid profile, fasting blood sugar, glycated haemoglobin (HbA1c), blood urea, and blood pressure measurement. Results: In our study, only two systemic factors weighed in as predictors of macular oedema: Systolic hypertension and serum lipids. Subanalysis of the lipid fractions yielded two significant correlates of CSME: Total cholesterol and serum triglycerides. Conclusion: A multifaceted healthcare team approach is essential for the management of diabetic patients. Ophthalmologists should evaluate the lipid profile of all diabetic macular oedema (DME) patients. Physicians should promptly refer diabetic patients with deranged lipid profiles to ophthalmologists to look for DME and provide appropriate ophthalmic care.

Objective Methods Results Conclusions The objective of this work was to understand how triglyceride plant oils can deliver strength and softness benefits to hair by their penetration. These plant oils are complex mixtures of TAGs, so the initial studies performed were with pure TAGs and then these data compared to plant oils and their measured TAG compositions.LC–MS was used to identify the di and triglycerides in coconut oil, Camellia oleifera oil and safflower seed oil. Penetration of these plant oils and pure individual triglycerides was measured by a differential extraction method. Cross‐sections of oils treated with 13C‐labelled triolein were studied by NanoSIMS to visualize location of triglyceride inside hair. Fatigue strength was measured using constant stress to generate a survival distribution. Models of the lipid‐rich cell membrane complex (CMC) were created with the equimolar ratio of 18‐methyl‐eicosanoic acid (MEAS), palmitic acid (C16:0) and oleic acid (C18:1).Penetration of the individual pure TAGs was confirmed for all chain lengths and degree of unsaturation tested with higher penetration for shorter chain lengths and unsaturated fatty acids. Detailed compositional analysis of selected plant oils showed a wide variety of TAGs and penetration was also demonstrated for these oils. NanoSIMS and modelling confirmed these TAGs are penetrating the lipid‐rich CMC of hair and are interacting with the fatty acids that make up the CMC. All plant oils delivered a fatigue strength improvement by penetration into the CMC and it is proposed that these oils prevent formation and/or propagation of flaws in the CMC network that leads to breakage.Many plant oils with a wide range of triglyceride compositions can penetrate into hair and NanoSIMS data confirmed these oils partition into the lipid‐rich cell membrane complex. Penetration studies of individual TAGs shown to be present in these oils confirmed TAGs of varying chain length can penetrate and there is a correlation between increased penetration efficacy and shorter chain lengths and presence of unsaturation in the fatty acid chains. All the oils studied delivered single fibre fatigue strength benefits. [ABSTRACT FROM AUTHOR]

Background: The triglyceride-glucose (TyG) index is a risk marker for arterial stiffness; however, the extent to which the TyG index is associated with arterial stiffness via lipids and inflammation remains unknown. The first aim was to probe the relationship between the TyG index and arterial stiffness in two surveys. The second aim was to clarify whether lipids and inflammation mediate this relationship. Methods: The sample size of 13,726 U.S. individuals from the National Examination Survey (NHANES) and 3,964 Chinese individuals from the China Health and Retirement Longitudinal Study (CHARLS 2015) were enrolled. Weighted multivariate logistic and linear regression models, as well as restricted cubic spline (RCS) and mediation analyses, were utilized to estimate complex relationships between the TyG index, arterial stiffness, lipids (non-high-density lipoprotein cholesterol [non-HDL-C]) and inflammation (C-reactive protein [CRP]) biomarkers. Results: A total of 3,420 U.S. patients and 992 Chinese patients were diagnosed with increased arterial stiffness. Regression analyses demonstrated that higher quartiles of the TyG index were associated with a greater incidence of increased arterial stiffness (NHANES: OR = 2.610, 95% CI = 2.043–3.334, P < 0.001; CHARLS: OR = 1.579, 95% CI = 1.057–2.360, P < 0.001). Participants with a higher TyG index/higher CRP level or with a higher TyG index/higher non-HDL-C level had the highest incidence of increased arterial stiffness in the two surveys. The results were still consistent when the sensitivity analysis was implemented with stricter clinical cut-off values of non-HDL-C. Mediation analysis verified that lipids (mediated effect: β = 0.012, P < 0.001 in NHANES; β = 0.020, P < 0.001 in CHARLS) and inflammation (mediated effect: β = 0.003, P < 0.001 in NHANES; β = 0.006, P < 0.001 in CHARLS) partially mediated this relationship. Conclusions: These results indicated a positive linear correlation between the TyG index, non-HDL-C level, CRP level and increased arterial stiffness in two surveys. Furthermore, lipids and inflammation could partly mediate the correlation of the TyG index with arterial stiffness in both surveys. [ABSTRACT FROM AUTHOR]

Background: The dietary inflammatory index (DII) serves as a tool to assess the inflammatory impact of an individual's diet. This study aimed to investigate the association between DII and some cardio-metabolic risk indices among patients with T2DM. Methods: Data from the Hoveyzeh Cohort Study, encompassing 2045 adults with T2DM, were analyzed. DII scores were calculated based on food frequency questionnaires. Anthropometric measurements and biochemical tests were performed to assess cardio-metabolic risk factors. Results: Higher DII scores were positively associated with elevated triglyceride levels, triglyceride-glucose (TyG) index, lipid accumulation product (LAP), anthropometric indices including a body shape index (ABSI), body roundness index (BRI), body mass index (BMI), hip, waist circumferences (WC), and waist-to-height ratio (all Ptrend < 0.05). Notably, no significant association was observed between DII and fasting blood sugar (FBS) levels (Ptrend > 0.05). Additionally, dietary intake analysis revealed a negative correlation between DII scores and intake of fiber, fruits, vegetables, legumes, fish, seafood, dairy products, magnesium, and vitamins A, C, D, and E (all Ptrend < 0.05). Conversely, higher DII scores were associated with increased consumption of red meat, processed meat, refined cereals, potatoes, and soft drinks (all Ptrend < 0.05). Conclusion: This study underscores the critical link between dietary inflammation, assessed by the DII score, and a multitude of cardio-metabolic risk factors in patients with T2DM. Notably, while the study did not find a significant association between DII and fasting blood sugar levels, it identified robust associations with novel anthropometric and biochemical indices indicative of cardio-metabolic risk. These findings highlight the potential of dietary interventions as a cornerstone strategy for managing T2DM and mitigating its associated complications. [ABSTRACT FROM AUTHOR]

Obesity is a threat to public health and effective new medications are required. Platycodonis Radix (PR) is a traditional medicinal/dietary plant with activities against obesity. Using mice given a diet rich in fat, the antiobesity components of PR were identified and their molecular mechanisms were clarified further in this investigation. Initially, the impacts of PR fractions on liver histology and biochemical markers were assessed. Subsequently, the degrees of lipogenic and lipolytic gene and protein expressions were determined. Oral administration of PR polysaccharides (PG) (0.80 g/kg body weight) improved liver function (alanine aminotransferase and aspartate aminotransferase) and its antioxidant activities (total superoxide dismutase, glutathione peroxidase, and malondialdehyde), as well as alleviated blood lipid (total cholesterol, total triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) values, inflammatory systemic (TNF-α and IL-1β), and histological abnormalities within the liver. Furthermore, PG administration downregulated the expression for lipogenic genes (ACC and FAS) and upregulated the expression for the lipolytic gene (PPARα, LPL, CPT1, and HSL). Importantly, PG raised AMPK phosphorylation and decreased SREBP-1c protein synthesis. Thus, it is possible that PG stimulates the AMPK-LPL/HSL path (lipolytic route) plus the AMPK-ACC/PPARα-CPT1 path (associated to β-oxidation of fatty acids), while inhibiting the AMPK/(SREBP-1c)-ACC/FAS path (lipogenic route). In summary, PG has the ability to regulate lipid metabolism, and it may be useful to pharmacologically activate AMPK with PG to prevent and cure obesity. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD). Methods: The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry. Results: After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group (P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group (P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group (P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92). Conclusions: Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management. [ABSTRACT FROM AUTHOR]

Background: Alterations in the secretion and composition of skin surface lipids (SSL) are closely associated with the development of acne. Lipidomics is a useful tool to analyse the SSL of different types of acne. Our previous study found that phosphatidylserine and triacylglycerols dominate SSL changes in male acne and infantile acne, respectively. However, skin surface lipids as well as specific lipids in female acne patients remain to be investigated. Objectives: To analyse and compare the SSL profile of acne women and healthy women and to discuss the involvement of differential lipids in acne development. Methods: Systematic lipidomics approach (high‐throughput UPLC‐QTOF‐MS technology in combination with multivariate data analysis methods) was used to analyse the variations of SSL between acne and healthy groups. Results: Analysis revealed significant differences in lipid content and composition between the two groups. Further analysis showed that levels of 13 individual lipids were significantly different and followed the same trend as the main class and subclasses. The largest individual contributor to the subgroup was triglycerides (TG) and phosphatidylinositol (PI). In addition, female acne patients exhibited reduced ceramide chain length (CCL) and increased levels of unsaturated fatty acids (UFAs), The changes of CCL in female acne are identical to male acne. Conclusions: There was a significantly higher level of TG and PI in the SSL of female acne patients. A reduction in CCL and an increase in UFAs content might contribute to the reduced skin barrier function in acne patients. The results suggest that female acne may have different pathogenesis than male acne. [ABSTRACT FROM AUTHOR]

Background Down syndrome (DS) is the most prevalent chromosomal disorder, being the leading cause of intellectual disability. The increased life expectancy of individuals with DS has led to a shift in the incidence of non-communicable chronic diseases, resulting in new concerns, particularly cardiovascular disease (CVD) and Alzheimer's disease. This study aimed to analyse the blood lipid profile of a large DS cohort to establish a baseline for evaluating health risk parameters. Methods A comprehensive literature search was conducted on PubMed and Virtual Health Library databases to identify original articles published before July 2022. Selected studies were included in the meta-analysis. Results Fifteen studies reporting serum lipid levels in individuals with DS were incorporated into the analysis. The meta-analysis used the means and standard deviations extracted from the selected studies. The analysis encompassed 671 participants in the DS group and 898 euploid controls. The results indicated significant differences in total cholesterol [C] (mean difference [MD]: −3.34; CI: 95%: −4.94 to −1.73; P < 0.0001), HDL-C (MD: −3.39; CI: 95%: −6.72 to −0.06; P = 0.05) and triglycerides (MD: 21.48; CI: 95%: 9.32 to 33.65; P = 0.0005) levels between individuals with DS and their control counterparts. Conclusions Individuals with DS have less favourable blood lipid concentrations than their controls, particularly HDL-C, triglycerides, and total-C, even when grouped by age. These findings underscore the importance of closer monitoring of lipid profiles in people with DS and the necessity for specific cut-offs for this population, considering the risk for ischemic heart and Alzheimer's diseases. [ABSTRACT FROM AUTHOR]

Lipids are crucial substances for the formation and retention of volatile compounds (VOCs). The lipid and VOC profiles of boiled donkey meat were investigated by lipidomics and volatilomics. In total, 4277 lipids belonging to 39 subclasses were identified, comprising 26.93% triglycerides (TGs), 15.74% phosphatidylcholins (PCs), and 9.40% phosphatidylethanolamines. The relative percentage of TG in the meat significantly decreases (p < 0.001) from 0 to 40 min, after which there is no significant change, whereas PCs, sphingomyelins, and methyl phosphatidylcholines (MePCs) show the opposite trend. TG(16:1_18:1_18:2) and TG(16:0_16:1_18:2) appear to be key lipids for retaining VOCs in boiled donkey meat. Furthermore, PC(18:3e_16:0) and MePC(31:0e) were found to be potential markers for discriminating donkey meat. A total of 83 VOCs were detected, including 25.30% aldehydes, 18.07% hydrocarbons, 14.46% ketones, and 13.25% alcohols. Eleven characteristic VOCs with relative odor activity values >1 were identified as the predominant flavor compounds in boiled donkey meat, mainly hexanal and 1‐octen‐3‐ol. Of the 258 differential lipids, 72 of them, especially polyunsaturated‐fatty acid–rich lipids, are the main contributors to the formation of VOCs. Together, the key lipids for retention and formation of VOCs in donkey meat were revealed, providing a theoretical basis for VOC regulation. [ABSTRACT FROM AUTHOR]

Vitamin B7(biotin) is not synthesized in our body and is retrieved from some food products like eggs, liver, pork and leafy vegetables and as well as microbes of gut. Deficiency of biotin majorly leads to loss of hair, rashes over skin, lethargy and seizures. It is noted that biotin is an anti-oxidant and negates free radical effects. Biotin is also involved in carbon dioxide metabolism and it might alter seizure threshold. Studies also suggest its effect on lipid metabolism as well. So, the primary objective of this study was to assess the efficacy of biotin in maximal electric shock (MES) induced generalized tonic-clonic seizures (GTCS) and pentylenetetrazole (PTZ) induced absence seizures. The secondary objective is to study the effect of combined treatment of biotin and sodium valproate on seizures as well as plasma lipid profile in rats. In our study 30 albino Wistar rats each were used in MES and PTZ model respectively. 30 rats were divided equally into following groups: I – distilled water (negative control) II – distilled water (positive control) III – sodium valproate (300 mg/kg) IV – biotin (10 mg/kg/day) V – biotin (10 mg/kg) + sodium valproate (150 mg/kg). We observed that the tonic hind limb extension was significantly reduced in the treatment group in MES model. Nitric oxide levels were also seen raised in combination group in MES model and all the treated groups in PTZ model. Biotin treated group showed increased high-density lipoproteins and reduced low density lipoproteins and triglycerides. Biotin had an additive effect to sodium valproate in both the models of epilepsy in rats. Further, it was also able to counteract hyperlipidemia cause by sodium valproate. [ABSTRACT FROM AUTHOR]