The nutrient sensor OGT in PVN neurons regulates feeding

Lagerlöf O, Slocomb JE, Hong I, Aponte Y, Blackshaw S, Hart GW, Huganir RL. Science. 2016 Mar 18;351(6279):1293-6. doi: 10.1126/science.aad5494. PMID: 26989246

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-GlcNAc transferase (OGT) catalyzes the posttranslational modification of proteins by O-GlcNAc 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-GlcNAcylation in αCaMKII neurons of the PVN as an important molecular mechanism that regulates feeding behavior.