Format

Send to

Choose Destination
Nat Commun. 2018 Nov 30;9(1):5103. doi: 10.1038/s41467-018-07461-x.

Adipocyte OGT governs diet-induced hyperphagia and obesity.

Author information

1
Program in Integrative Cell Signaling and Neurobiology of Metabolism and Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.
2
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, 06520, USA.
3
Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
4
Cardiovascular, Metabolic & Endocrine Disease Research Unit, Pfizer Worldwide Research & Development, Cambridge, MA, 02139, USA.
5
Department of Genetics and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520, USA.
6
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
7
Department of Statistics, Pennsylvania State University, University Park, PA, 16802, USA.
8
Program in Integrative Cell Signaling and Neurobiology of Metabolism and Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA. xiaoyong.yang@yale.edu.
9
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, 06520, USA. xiaoyong.yang@yale.edu.

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.

PMID:
30504766
PMCID:
PMC6269424
DOI:
10.1038/s41467-018-07461-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center