Influence of the Human Lipidome on Epicardial Fat Volume in Mexican American Individuals

Frontiers in Cardiovascular Medicine

Peter J. Meikle¹  Kevin Huynh¹  Corey Giles¹  Ravindranath Duggirala²  Marcio Almeida²  Vincent P. Diego²  Mikko Kuokkanen²  Joanne E. Curran²  Ana Cristina Leandro²  John Blangero²  Geoffrey D. Clarke³  Laura F. Michael⁴  Thy Duong⁵ 

[1] Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC, Australia;Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, United States;Department of Radiology and Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, United States;Eli Lilly and Company, Indianapolis, IN, United States;Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia;

关键词: cardiovascular disease;    lipidomic profiles;    epicardial fat volume;    Mexican Americans;    CMRI;   

DOI  :  10.3389/fcvm.2022.889985

来源: DOAJ

【 摘 要 】

IntroductionCardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma lipids on EAT volume.AimThe focus of this study is on the identification of novel lipidomic species associated with CMRI-derived measures of epicardial fat in Mexican American individuals.MethodsWe performed lipidomic profiling on 200 Mexican American individuals. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing measures of 799 unique species from circulating plasma samples. Because of our extended pedigree design, we utilized a standard quantitative genetic linear mixed model analysis to determine whether lipids were correlated with EAT by formally testing for association between each lipid species and the CMRI epicardial fat phenotype.ResultsAfter correction for multiple testing using the FDR approach, we identified 135 lipid species showing significant association with epicardial fat. Of those, 131 lipid species were positively correlated with EAT, where increased circulating lipid levels were correlated with increased epicardial fat. Interestingly, the top 10 lipid species associated with an increased epicardial fat volume were from the deoxyceramide (Cer(m)) and triacylglycerol (TG) families. Deoxyceramides are atypical and neurotoxic sphingolipids. Triacylglycerols are an abundant lipid class and comprise the bulk of storage fat in tissues. Pathologically elevated TG and Cer(m) levels are related to CVD risk and, in our study, to EAT volume.ConclusionOur results indicate that specific lipid abnormalities such as enriched saturated triacylglycerols and the presence of toxic ceramides Cer(m) in plasma of our individuals could precede CVD with increased EAT volume.

【 授权许可】

Unknown