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Genome-wide changes in OGT-depleted mouse adipose tissue

ABSTRACT: Appetite control is key to combat obesity in an over-nutritious environment. Whether and how over-nutrition induces hyperphagia and obesity through the adipose-to-brain axis is unclear. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues. Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake. Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of anandamide (AEA), an endogenous appetite-inducing cannabinoid (CB). Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner. These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis that induces hyperphagia and obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE111735 | GEO | 2018/09/12

REPOSITORIES: GEO

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