O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity

Yunfan Yang, Minnie Fu, Min-Dian Li, Kaisi Zhang, Bichen Zhang, Simeng Wang, Yuyang Liu, Weiming Ni, Qunxiang Ong, Jia Mi and Xiaoyong Yang ()
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Yunfan Yang: Yale University School of Medicine
Minnie Fu: Yale University School of Medicine
Min-Dian Li: Yale University School of Medicine
Kaisi Zhang: Yale University School of Medicine
Bichen Zhang: Yale University School of Medicine
Simeng Wang: Yale University School of Medicine
Yuyang Liu: Yale University School of Medicine
Weiming Ni: Yale University School of Medicine
Qunxiang Ong: Yale University School of Medicine
Jia Mi: Yale University School of Medicine
Xiaoyong Yang: Yale University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Excessive visceral fat accumulation is a primary risk factor for metabolically unhealthy obesity and related diseases. The visceral fat is highly susceptible to the availability of external nutrients. Nutrient flux into the hexosamine biosynthetic pathway leads to protein posttranslational modification by O-linked β-N-acetylglucosamine (O-GlcNAc) moieties. O-GlcNAc transferase (OGT) is responsible for the addition of GlcNAc moieties to target proteins. Here, we report that inducible deletion of adipose OGT causes a rapid visceral fat loss by specifically promoting lipolysis in visceral fat. Mechanistically, visceral fat maintains a high level of O-GlcNAcylation during fasting. Loss of OGT decreases O-GlcNAcylation of lipid droplet-associated perilipin 1 (PLIN1), which leads to elevated PLIN1 phosphorylation and enhanced lipolysis. Moreover, adipose OGT overexpression inhibits lipolysis and promotes diet-induced obesity. These findings establish an essential role for OGT in adipose tissue homeostasis and indicate a unique potential for targeting O-GlcNAc signaling in the treatment of obesity.

Date: 2020
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DOI: 10.1038/s41467-019-13914-8

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