Back to Search
Start Over
O-GlcNAc transferase inhibits visceral fat lipolysis and promotes diet-induced obesity.
- Source :
-
Nature communications [Nat Commun] 2020 Jan 10; Vol. 11 (1), pp. 181. Date of Electronic Publication: 2020 Jan 10. - Publication Year :
- 2020
-
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.
- Subjects :
- Acetylglucosamine metabolism
Animals
Cell Line, Tumor
Fasting
Gene Deletion
HEK293 Cells
HeLa Cells
Homeostasis
Humans
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
N-Acetylglucosaminyltransferases genetics
Perilipin-1 metabolism
Phosphorylation
Protein Processing, Post-Translational
Signal Transduction
Diet adverse effects
Intra-Abdominal Fat drug effects
Lipolysis drug effects
N-Acetylglucosaminyltransferases antagonists & inhibitors
Obesity metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31924761
- Full Text :
- https://doi.org/10.1038/s41467-019-13914-8