ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026
Gut Microbiota Modulate Adipose Eicosanoid Metabolism: Potential Roles of the Lipoxygenase Pathway.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026. 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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Abstract
Numerous studies support that gut microbiota regulate adipose inflammation and function, thereby influencing the development of obesity, diabetes, and associated metabolic disorders; however, the underlying mechanisms remain not fully elucidated. While previous studies on microbiota-adipose interactions have primarily focused on how gut microbiota modulate adipose protein-based mediators, the role of lipid mediators (LMs), lipid-based signaling molecules crucial for adipose homeostasis, remains unclear. In this study, we used high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted lipidomics, which can quantify over 100 LMs, to compare LM profiles in adipose tissues from germ-free (GF) and conventionally raised (specific pathogen-free, SPF) mice. We found that 5- and 12/15-lipoxygenase (LOX)-derived LMs were among the most significantly altered metabolites in conventionally raised mice compared to GF controls. Mechanistically, the effects of the gut microbiota are associated with two potential pathways: (1) downregulating transcriptional expression of 5- and 12/15-LOX in adipose tissue, and (2) lowering circulating levels of 5- and 12/15-LOX-derived metabolites. Given the potent biological activities of LOX-derived LMs, these findings may suggest a novel mechanism by which gut microbiota modulate adipose function and influence disease development.
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