The circulating lipidome in severe obesity
Abstract
Severe obesity (SevO; BMI ≥ 40 kg/m 2 ) is rising globally yet remains understudied mechanistically. To characterize lipidomic alterations at the species level, we analyzed Border Health Research Cohort participants with fasting plasma lipidomics and genetic data, comparing SevO ( n = 185) to non-obese controls (18.5 ≥ BMI < 25; n = 393). We quantified 830 lipid species across 49 classes and assessed associations using logistic regression, orthogonal projections to latent structures discriminant analysis (OPLS-DA), and network deconvolution Mendelian randomization (NDMR). SevO participants showed more adverse cardiometabolic traits. Lipidomics revealed broad dysregulation: shorter, saturated, and monounsaturated triacylglycerols were elevated in individuals living with SevO compared to controls, while lysophospholipids, plasmalogens, cholesteryl esters, and long-chain species were reduced. OPLS-DA identified over 300 lipids strongly predictive of SevO, and NDMR implicated specific triacylglycerols as potentially contributing to SevO status. Influential lipids correlated with insulin resistance, liver fat, body composition, and high-density lipoprotein cholesterol (HDL-C). Short-chain triacylglycerols emerged as a distinctive, consistently elevated SevO signature.
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Authors: Mohammad Yaser Anwar, Heather M. Highland, Alexandra B. Palmer, Thy Duong, Zhaotong Lin, Wanying Zhu, Jessica Sprinkles, Daeeun Kim, Kristin L. Young, Hung-Hsin Chen, Mohanraj Krishnan, Absalon Gutierrez, Rashedeh Roshani, Elizabeth G. Frankel, Joshua M. Landman, Penny Gordon‐Larsen, Susan K. Fried, Miryoung Lee, Susan P. Fisher‐Hoch, Joseph McCormick, Joanne Curran, John Blangero, Peter J. Meikle, Corey Giles, Jennifer Elizabeth Below, K.E. North, Mariaelisa Graff
Institutions: Icahn School of Medicine at Mount Sinai, University of North Carolina at Chapel Hill, Vanderbilt University, La Trobe University, Florida State University, Baker Heart and Diabetes Institute, Pennsylvania State University, Vanderbilt University Medical Center, The University of Texas Rio Grande Valley, The University of Texas Health Science Center at Houston, Academia Sinica, Institute of Biomedical Sciences, Academia Sinica