ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx
Year: 2024
Type: article
Study design: Observational Study
Abstract: Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. BAT is activated by 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with BMI and which directly improves metabolism in multiple tissues. Here we profile plasma lipidomics from a cohort of 83 people and test which lipids’ association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME both replicably inversely associate with BMI and mechanistically activate calcium fluxes in mouse brown and white adipocytes in vitro, which implicates this pathway and 9,10-diHOME as candidate therapeutic targets. ScreenDMT can be applied to test directional mediation, directional replication, and qualitative interactions, such as identifying biomarkers whose association is shared (replication) or opposite (qualitative interaction) across diverse populations.
Source: Communications Biology
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Awards: Fibroblast Growth Factor and Energy Metabolism, The Lipidomics of Adipose Tissue Thermogenesis, G3057836367, G3907630707, G5850682332, IDENTIFICATION OF NOVEL LIPID MEDIATORS WITH ANTI-DIABETIC EFFECT, Role of brown fat-derived specialized pro-resolving lipid mediators in inflammation and metabolism, Telomerase as a Marker of Brown and White Adipose Tissue Stem Cells, Training Grant in Diabetes and Metabolism, Diabetes Research Center, Dissecting the thermogenic adipose niche
OpenAlex ID: W4401562067