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View Full TextWhen enough isn't enough
Overeating and obesity are rapidly becoming worldwide problems. Normally, mice do not overeat—they balance their caloric intake with their caloric needs. Lagerlöf et al. deleted an enzyme called O-GlcNAc transferase (OGT) from a subset of neurons in the mouse hypothalamus (see the Perspective by Schwartz). After the loss of OGT, the animals began to overeat and rapidly gained weight. The animals ate more at meal times, rather than eating more often. Thus, OGT seems to regulate satiety and helps to couple caloric intake to caloric need.
Abstract
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.
