Adipocyte OGT governs diet-induced hyperphagia and obesity.

Nature communications 2018 Nov 30

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Palatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity. Whether and how overnutrition increases appetite 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. Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases. 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 N-arachidonyl ethanolamine (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 to induce hyperphagia and obesity.

Citation

Min-Dian Li, Nicholas B Vera, Yunfan Yang, Bichen Zhang, Weiming Ni, Enida Ziso-Qejvanaj, Sheng Ding, Kaisi Zhang, Ruonan Yin, Simeng Wang, Xu Zhou, Ethan X Fang, Tian Xu, Derek M Erion, Xiaoyong Yang. Adipocyte OGT governs diet-induced hyperphagia and obesity. Nature communications. 2018 Nov 30;9(1):5103