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Dreyfuss, J.M.* ; Djordjilović, V.* ; Pan, H.* ; Bussberg, V.* ; MacDonald, A.M.* ; Narain, N.R.* ; Kiebish, M.A.* ; Blüher, M. ; Tseng, Y.H.* ; Lynes, M.D.*

ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx.

Comm. Biol. 7:996 (2024)

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	Open Access Gold

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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 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 are both replicably inversely associated with BMI and mechanistically activate calcium influx in mouse brown and white adipocytes in vitro, which implicates this signaling 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Conjugated Linoleic-acid; Lipokine 12,13-dihome; Brown Fat; Mediation

ISSN (print) / ISBN 2399-3642

e-ISSN 2399-3642

Journal Communications Biology

Quellenangaben Volume: 7, Issue: 1, Article Number: 996

Publisher Springer

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants NIH fellowships
US Army Medical Research
U.S. National Institutes of Health (NIH)
United States Department of Defense | U.S. Army (United States Army)