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Kabra, D.G. ; Pfuhlmann, K. ; García-Cáceres, C. ; Schriever, S.C. ; Casquero García, V. ; Kebede, A.F.* ; Fuente-Martin, E. ; Trivedi, C.* ; Heppner, K.* ; Uhlenhaut, N.H. ; Legutko, B. ; Kabra, U.D. ; Gao, Y. ; Yi, C.-X. ; Quarta, C. ; Clemmensen, C. ; Finan, B. ; Müller, T.D. ; Meyer, C.W. ; Paez-Pereda, M.* ; Stemmer, K. ; Woods, S.C.* ; Perez-Tilve, D.* ; Schneider, R.* ; Olson, E.N.* ; Tschöp, M.H. ; Pfluger, P.T.

Hypothalamic leptin action is mediated by histone deacetylase 5.

Nat. Commun. 7:10782 (2016)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Green Fluorescent Protein; Nervous-system Control; Insulin-resistance; Proopiomelanocortin Neurons; Glucose-homeostasis; Physical-activity; Gene-expression; Deficient Mice; Pomc Neurons; Obesity
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 10782 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Diabetes and Cancer (IDC)
Institute of Functional Epigenetics (IFE)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502294-001
G-502200-001
G-501900-221
G-501900-227
G-502800-001
PubMed ID 26923837
DOI 10.1038/ncomms10782
WOS ID WOS:000371040600003
Scopus ID 84959422001
Erfassungsdatum 2016-03-07
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