The nutrient sensor OGT in PVN neurons regulates feeding

• Published in: Science (American Association for the Advancement of Science) Vol. 351; no. 6279; pp. 1293 - 1296
• Main Authors: Lagerlöf, Olof, Slocomb, Julia E., Hong, Ingie, Aponte, Yeka, Blackshaw, Seth, Hart, Gerald W., Huganir, Richard L.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 18.03.2016; The American Association for the Advancement of Science
• Subjects: Acetylglucosamine - metabolism; Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Eating Habits; Energy Metabolism - genetics; Energy Metabolism - physiology; Feeding Behavior - physiology; Gene Deletion; Homeostasis - genetics; Hyperphagia - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; N-Acetylglucosaminyltransferases - genetics; N-Acetylglucosaminyltransferases - physiology; Neurons - enzymology; Obesity; Obesity - genetics; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - enzymology; Paraventricular Hypothalamic Nucleus - physiology; Protein Processing, Post-Translational; Satiety Response - physiology
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aad5494

Maintaining energy homeostasis is crucial for the survival and health of organisms. The brain regulates feeding by responding to dietary factors and metabolic signals from peripheral organs. It is unclear how the brain interprets these signals. O-GIcNAc transferase (OGT) catalyzes the posttranslational modification of proteins by O-GIcNAc and is regulated by nutrient access. Here, we show that acute deletion of OGT from αCaMKII-positive neurons in adult mice caused obesity from overeating. The hyperphagia derived from the paraventricular nucleus (PVN) of the hypothalamus, where loss of OGT was associated with impaired satiety. These results identify O-GIcNAcylation in αCaMKII neurons of the PVN as an important molecular mechanism that regulates feeding behavior.