Journal Article

Adipocyte OGT governs diet-induced hyperphagia and obesity

Zhang, Kaisi, Zhou, Xu, Ziso-Qejvanaj, Enida, Wang, Simeng, Ni, Weiming, Li, Min-Dian, Fang, Ethan X., Xu, Tian, Vera, Nicholas B., Yang, Xiaoyong, Erion, Derek M., Yang, Yunfan, Yin, Ruonan, Ding, Sheng, Zhang, Bichen

2018

Overview

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. Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/106 / 38/39 / 38/70 / 38/77 / 59/57 / 631/443/319/1488 / 631/443/319/2723 / 631/45/221 / 64/60 / 82/1 / 82/80 / Acetylglucosamine - metabolism / Adipocytes / Adipocytes - metabolism / Adipose Tissue - metabolism / Adipose Tissue - pathology / Animals / Appetite / Blotting, Western / Body Weight - genetics / Body Weight - physiology / Brain / Cannabinoids / Cannabinoids - metabolism / Cell Line / Desaturation / Diet / Ethanolamine / Food intake / High fat diet / Humanities and Social Sciences / Humans / Hyperphagia / Hyperphagia - metabolism / Hyperphagia - pathology / In Vitro Techniques / Intracellular signalling / Lipids / Male / Metabolic disorders / Mice / Mice, Inbred C57BL / multidisciplinary / N-Acetylglucosamine / O-GlcNAcylation / Obesity / Obesity - metabolism / Obesity - pathology / Overnutrition / Pharmacology / Proteins / Real-Time Polymerase Chain Reaction / Science / Science (multidisciplinary) / Serine / Threonine / Transcription activation