@article{9812cb1df9ca4605a29cb46b8db73aa5,
title = "Hypothalamic leptin action is mediated by histone deacetylase 5",
abstract = "Hypothalamic leptin signalling has a key role in food intake and energy-balance control and is often impaired in obese individuals. Here we identify histone deacetylase 5 (HDAC5) as a regulator of leptin signalling and organismal energy balance. Global HDAC5 KO mice have increased food intake and greater diet-induced obesity when fed high-fat diet. Pharmacological and genetic inhibition of HDAC5 activity in the mediobasal hypothalamus increases food intake and modulates pathways implicated in leptin signalling. We show HDAC5 directly regulates STAT3 localization and transcriptional activity via reciprocal STAT3 deacetylation at Lys685 and phosphorylation at Tyr705. In vivo, leptin sensitivity is substantially impaired in HDAC5 loss-of-function mice. Hypothalamic HDAC5 overexpression improves leptin action and partially protects against HFD-induced leptin resistance and obesity. Overall, our data suggest that hypothalamic HDAC5 activity is a regulator of leptin signalling that adapts food intake and body weight to our dietary environment.",
author = "Kabra, {Dhiraj G.} and Katrin Pfuhlmann and Cristina Garc{\'i}a-C{\'a}ceres and Schriever, {Sonja C.} and Garc{\'i}a, {Veronica Casquero} and Kebede, {Adam Fiseha} and Esther Fuente-Martin and Chitrang Trivedi and Kristy Heppner and Uhlenhaut, {N. Henriette} and Beata Legutko and Kabra, {Uma D.} and Yuanqing Gao and Yi, {Chun Xia} and Carmelo Quarta and Christoffer Clemmensen and Brian Finan and M{\"u}ller, {Timo D.} and Meyer, {Carola W.} and Marcelo Paez-Pereda and Kerstin Stemmer and Woods, {Stephen C.} and Diego Perez-Tilve and Robert Schneider and Olson, {Eric N.} and Tsch{\"o}p, {Matthias H.} and Pfluger, {Paul T.}",
note = "Funding Information: We thank Marlene Kilian, Daniela Heine, Laura Sehrer, Jazzminn Hembree and Nickki Ottaway for excellent technical assistance. We would like to thank Professor Jeff Molkentin for providing control and HDAC5–GFP adenoviruses. We further thank Professor Randy Seeley and Silke Morin for scientific advice and help in preparing the manuscript. The work was funded in part by the Helmholtz Alliance ICEMED—Imaging and Curing Environmental Metabolic Diseases, by the Center for Diabetes Research (DZD e. V.), by the FP7-HEALTH-2009-241592 EurOCHIP grant, and by the Helmholtz Portfolio Theme {\textquoteleft}Metabolic Dysfunction and Common Disease{\textquoteright}.",
year = "2016",
month = feb,
day = "29",
doi = "10.1038/ncomms10782",
language = "English (US)",
volume = "7",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}