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, Xingyan Ethan Fang, Tian Xu, Derek M. Erion, Xiaoyong Yang

Research output: Contribution to journalArticle

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
Externally publishedYes

Fingerprint

obesity
diets
Hyperphagia
fats
Nutrition
Adipocytes
Obesity
Diet
brain
lipids
metabolic diseases
food intake
desaturation
Fats
Appetite
cues
nutrients
Brain
food
Overnutrition

ASJC Scopus subject areas

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

Cite this

Li, M. D., Vera, N. B., Yang, Y., Zhang, B., Ni, W., Ziso-Qejvanaj, E., ... 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

Adipocyte OGT governs diet-induced hyperphagia and obesity. / Li, Min Dian; Vera, Nicholas B.; Yang, Yunfan; Zhang, Bichen; Ni, Weiming; Ziso-Qejvanaj, Enida; Ding, Sheng; Zhang, Kaisi; Yin, Ruonan; Wang, Simeng; Zhou, Xu; Fang, Xingyan Ethan; Xu, Tian; Erion, Derek M.; Yang, Xiaoyong.

In: Nature communications, Vol. 9, No. 1, 5103, 01.12.2018.

Research output: Contribution to journalArticle

Li, MD, Vera, NB, Yang, Y, Zhang, B, Ni, W, Ziso-Qejvanaj, E, Ding, S, Zhang, K, Yin, R, Wang, S, Zhou, X, Fang, XE, Xu, T, Erion, DM & Yang, X 2018, 'Adipocyte OGT governs diet-induced hyperphagia and obesity', Nature communications, vol. 9, no. 1, 5103. https://doi.org/10.1038/s41467-018-07461-x
Li MD, Vera NB, Yang Y, Zhang B, Ni W, Ziso-Qejvanaj E et al. Adipocyte OGT governs diet-induced hyperphagia and obesity. Nature communications. 2018 Dec 1;9(1). 5103. https://doi.org/10.1038/s41467-018-07461-x
Li, Min Dian ; Vera, Nicholas B. ; Yang, Yunfan ; Zhang, Bichen ; Ni, Weiming ; Ziso-Qejvanaj, Enida ; Ding, Sheng ; Zhang, Kaisi ; Yin, Ruonan ; Wang, Simeng ; Zhou, Xu ; Fang, Xingyan Ethan ; Xu, Tian ; Erion, Derek M. ; Yang, Xiaoyong. / Adipocyte OGT governs diet-induced hyperphagia and obesity. In: Nature communications. 2018 ; Vol. 9, No. 1.
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