Adipocyte OGT governs diet-induced hyperphagia and obesity

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

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number5103
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Li, M. D., Vera, N. B., Yang, Y., Zhang, B., Ni, W., Ziso-Qejvanaj, E., Ding, S., Zhang, K., Yin, R., Wang, S., Zhou, X., Fang, E. X., Xu, T., Erion, D. M., & Yang, X. (2018). Adipocyte OGT governs diet-induced hyperphagia and obesity. Nature communications, 9(1), [5103]. https://doi.org/10.1038/s41467-018-07461-x