The circulating lipidome in severe obesity
Abstract
Severe obesity (SevO; BMI ≥ 40 kg/m²) 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.
Related
- Comparative Effects and Dose–Response Relationships of Exercise Modalities on Resting Circulating Interleukin-6 in People with Overweight or Obesity: A Systematic Review and Dose–Response Network Meta-Analysis
- Untargeted Lipidomics Reveals Dynamic Changes to the HEK 293T Lipidome During Lentiviral Vector Production Over 72 Hours
- Adaptive drug resistance in melanoma is characterised by lipidome remodelling while maintaining cell membrane biophysical properties.
- tRNA regulatory ecosystem states shape tissue and circulating small-RNA landscapes in gastric cancer
- Circulating chromatin reveals effects of disease-associated variants on gene regulation
BibTeX
@article{anwar2026circulating,
title = {{The circulating lipidome in severe obesity}},
author = {Mohammad Yaser Anwar and Heather M. Highland and Alexandra B. Palmer and Thy Duong and Zhaotong Lin and Wanying Zhu and Jessica Sprinkles and Daeeun Kim and Kristin L. Young and Hung-Hsin Chen and Mohanraj Krishnan and Absalon Gutierrez and Rashedeh Roshani and Elizabeth G. Frankel and Joshua Landman and Penny Gordon-Larsen and Susan K. Fried and Miryoung Lee and Susan P. Fisher-Hoch and Joseph B. McCormick and Joanne Curran and John Blangero and Peter J. Meikle and Corey Giles and Jennifer E. Below and Kari E. North and Mariaelisa Graff},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117801},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03182-2},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - The circulating lipidome in severe obesity
AU - Mohammad Yaser Anwar
AU - Heather M. Highland
AU - Alexandra B. Palmer
AU - Thy Duong
AU - Zhaotong Lin
AU - Wanying Zhu
AU - Jessica Sprinkles
AU - Daeeun Kim
AU - Kristin L. Young
AU - Hung-Hsin Chen
AU - Mohanraj Krishnan
AU - Absalon Gutierrez
AU - Rashedeh Roshani
AU - Elizabeth G. Frankel
AU - Joshua Landman
AU - Penny Gordon-Larsen
AU - Susan K. Fried
AU - Miryoung Lee
AU - Susan P. Fisher-Hoch
AU - Joseph B. McCormick
AU - Joanne Curran
AU - John Blangero
AU - Peter J. Meikle
AU - Corey Giles
AU - Jennifer E. Below
AU - Kari E. North
AU - Mariaelisa Graff
PY - 2026
DA - 2026/10/08
JO - iScience
DO - 10.1016/j.isci.2026.117801
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03182-2
AB - Severe obesity (SevO; BMI ≥ 40 kg/m²) 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.
SN - 2589-0042
ER -