The circulating lipidome in severe obesity

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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Publication Details

Journal
iScience
Published
2026-10-09
DOI
https://doi.org/10.1016/j.isci.2026.117801
Primary Topic
Metabolomics and Mass Spectrometry Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

The circulating lipidome in severe obesity

Jessica Sprinkles, John Blangero, Peter J. Meikle, Zhaotong Lin et al.
iScience
Metabolomics and Mass Spectrometry Studies
article

The circulating lipidome in severe obesity

Jessica Sprinkles, John Blangero, Peter J. Meikle, Zhaotong Lin, Daeeun Kim, Susan P. Fisher‐Hoch, Penny Gordon‐Larsen, Jennifer Elizabeth Below, Alexandra B. Palmer, Corey Giles, Joshua M. Landman, Kristin L. Young, Thy Duong, Mariaelisa Graff, Mohammad Yaser Anwar, Miryoung Lee, Susan K. Fried, Heather M. Highland, Rashedeh Roshani, Mohanraj Krishnan, Joseph McCormick, K.E. North, Elizabeth G. Frankel, Hung-Hsin Chen, Wanying Zhu, Joanne Curran, Absalon Gutierrez
article en

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.

iScienceVol. 29(11)
Florida State University (US), University of North Carolina at Chapel Hill (US), Pennsylvania State University (US), Baker Heart and Diabetes Institute (AU), La Trobe University (AU), Vanderbilt University (US), The University of Texas Rio Grande Valley (US), Institute of Biomedical Sciences, Academia Sinica (TW), Academia Sinica (TW), Vanderbilt University Medical Center (US), The University of Texas Health Science Center at Houston (US), Icahn School of Medicine at Mount Sinai (US)
National Institute on Aging, National Human Genome Research Institute, National Center for Advancing Translational Sciences, National Center for Medical Rehabilitation Research, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NHLBI Division of Intramural Research, Division of Diabetes, Endocrinology, and Metabolic Diseases
Good health and well-being
Openalex Percentile: Top 23%
Metabolomics and Mass Spectrometry Studies
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