ArticlemedRxiv : the preprint server for health sciences2025
The Circulating Lipidome In Severe Obesity.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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26 authors.
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Abstract
Background: Severe obesity (SevO; BMI ≥40 kg/m Methods: We analyzed 578 participants from the Cameron County Hispanic Cohort (CCHC) with fasting plasma lipidomic and genetic data, comparing those living with SevO (n=185) to non-obese controls (n=393). A total of 830 circulating lipid species across 49 classes were quantified. Associations between individual lipids and SevO were assessed using logistic regression and orthogonal projections to latent structures discriminant analysis (OPLS-DA). Potential causal links were assessed using network deconvolution mendelian randomization (NDMR), and influential lipids were correlated with CMD traits and DXA-derived body composition. Results: Participants with SevO exhibited statistically significantly more adverse cardiometabolic risk factors than controls. Lipidomic profiling revealed broad alterations: shorter, saturated, and monounsaturated triacylglycerols were markedly elevated, while lysophospholipids, plasmalogens, cholesteryl esters, and long-chain lipids were reduced in individuals with SevO when compared to controls (BMI ≥ 18.5 and > 25 kg/m Conclusions: Our findings reveal that SevO is marked by extensive and lipid class-specific dysregulation of the circulating lipidome, with strong links to cardiometabolic risk. Notably, triacylglycerols containing shorter length acyl chains emerged as a distinctive lipid signature of SevO-consistently elevated, strongly discriminative of SevO status, and uniquely exhibiting a consistent causal relationship. Our results provide compelling evidence for a novel lipidomic pathway underpinning severe obesity and underscore critical avenues for future research into its genetic, dietary, and mechanistic determinants.
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