The nutrient sensor OGT in PVN neurons regulates feeding

Olof Lagerlöf; Julia E Slocomb; Ingie Hong; Yeka Aponte; Seth Blackshaw; Gerald W Hart; Richard L Huganir

doi:10.1126/science.aad5494

The nutrient sensor OGT in PVN neurons regulates feeding

Science. 2016 Mar 18;351(6279):1293-6. doi: 10.1126/science.aad5494.

Authors

Olof Lagerlöf¹, Julia E Slocomb², Ingie Hong³, Yeka Aponte⁴, Seth Blackshaw³, Gerald W Hart⁵, Richard L Huganir⁶

Affiliations

¹ 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.
² National Institute on Drug Abuse + National Institutes of Health/Johns Hopkins University Graduate Partnership Program, Baltimore, MD 21224, USA.
³ Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ 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.
⁵ Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁶ Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

MeSH terms

Acetylglucosamine / metabolism
Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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 / genetics
Paraventricular Hypothalamic Nucleus / cytology
Paraventricular Hypothalamic Nucleus / enzymology
Paraventricular Hypothalamic Nucleus / physiology*
Protein Processing, Post-Translational
Satiety Response / physiology

Substances

N-Acetylglucosaminyltransferases
O-GlcNAc transferase
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Acetylglucosamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding