@article{ac54af0111a546a79ec8fb6a115ffb12,
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 aCaMKII-positive neurons in adult mice caused obesity from overeating. The hyperphagia derived from the paraventricular nucleus (PVN) of the hypothalamus, where loss of OGTwas associated with impaired satiety. These results identify O-GlcNAcylation in aCaMKII neurons of the PVN as an important molecular mechanism that regulates feeding behavior.",
author = "Olof Lagerl{\"o}f and Slocomb, {Julia E.} and Ingie Hong and Yeka Aponte and Seth Blackshaw and Hart, {Gerald W.} and Huganir, {Richard L.}",
note = "Funding Information: We thank the many engineers who have contributed to the success of the New Horizons mission and NASA''s Deep Space Network for a decade of excellent support to New Horizons. We thank the reviewers for close and meticulous reading, and P. Engebretson for contribution to figure production. S.A.S. is also affiliated with Florida Space Institute, Uwingu LLC, Golden Spike Co., and World View Enterprises. H.J.R. is also affiliated with B612 Foundation and Cornell Technical Service. Supporting imagery is available in the supplementary materials. As contractually agreed to with NASA, fully calibrated New Horizons Pluto system data will be released via the NASA Planetary Data System at https://pds.nasa.gov/ in a series of stages in 2016 and 2017 as the data set is fully downlinked and calibrated. This work was supported by NASA''s New Horizons project. O.L., G.W.H., and R.L.H. designed all experiments; the optogenetics experiments were also designed by Y.A. and J.E.S., and the elecotrophysiological experiments were also designed by I.H. O.L. performed all experiments and analyzed all data but the electrophysiology (I.H.) and the optogenetics (J.E.S.). The optogenetics data were analyzed by J.E.S., Y.A., and O.L. O.L., G.W.H., and R.L.H. wrote the manuscript. We thank G. Sch{\"u}tz for providing the aCaMKII-CreERT2 mice, J. L. Bedont for help with in situ hybridization experiments, and R. H. White for assistance with mating and genotyping. All data necessary to understand and assess the conclusions of the manuscript are in the body of the paper and in the supplementary materials. All primary data are archived on a secure server located in the Department of Neuroscience at Johns Hopkins University (JHU). All data will be made available upon request. G.W.H. receives a share of royalty received by the university on sales of the CTD 110.6 antibody, which are managed by JHU. The research was supported by NIH (grant R01NS036715 to R.L.H. and grants R01DK6167, N01-HV-00240, and P01HL107153 to G.W.H.) and the National Institute on Drug Abuse Intramural Research Program (Y.A.).",
year = "2016",
month = mar,
day = "18",
doi = "10.1126/science.aad5494",
language = "English (US)",
volume = "351",
pages = "1293--1296",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6279",
}