title: The nutrient sensor OGT in PVN neurons regulates feeding.
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.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Olof
authors.initials: O
authors.lastname: Lagerlöf
authors.affiliation: National Institute on Drug Abuse + National Institutes of Health/Johns Hopkins University Graduate Partnership Program, Baltimore, MD 21224, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Slocomb
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Ingie
authors.initials: I
authors.lastname: Hong
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Intramural Research Program, Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Yeka
authors.initials: Y
authors.lastname: Aponte
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Hart
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. rhuganir@jhmi.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D017353:Gene Deletion; D006706:Homeostasis / Q000235:genetics; D006963:Hyperphagia / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000201:enzymology; D009765:Obesity / Q000235:genetics; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012528:Satiety Response / Q000502:physiology
chemical_list: D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000117:Acetylglucosamine