@article{5e74d0fb06894c26a19705f7e93ae842,
title = "SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance",
abstract = "Chronic feeding on high-calorie diets causes obesity and type 2 diabetes mellitus (T2DM), illnesses that affect hundreds of millions. Thus, understanding the pathways protecting against diet-induced metabolic imbalance is of paramount medical importance. Here, we show that mice lacking SIRT1 in steroidogenic factor 1 (SF1) neurons are hypersensitive to dietary obesity owing to maladaptive energy expenditure. Also, mutant mice have increased susceptibility to developing dietary T2DM due to insulin resistance in skeletal muscle. Mechanistically, these aberrations arise, in part, from impaired metabolic actions of the neuropeptide orexin-A and the hormone leptin. Conversely, mice overexpressing SIRT1 in SF1 neurons are more resistant to diet-induced obesity and insulin resistance due to increased energy expenditure and enhanced skeletal muscle insulin sensitivity. Our results unveil important protective roles of SIRT1 in SF1 neurons against dietary metabolic imbalance.",
author = "Giorgio Ramadori and Teppei Fujikawa and Jason Anderson and Berglund, {Eric D.} and Renata Frazao and Shaday Mich{\'a}n and Vianna, {Claudia R.} and Sinclair, {David A.} and Elias, {Carol F.} and Roberto Coppari",
note = "Funding Information: We thank Kristen Wertz for technical assistance; Joyce Repa (UTSW Medical Center, USA) for quantitative real time PCR primers; Yoshiyuki Horio (Sapporo Medical School, Japan) for the SIRT1 antibodies; Frederick Alt and Raul Mostoslavsky (Harvard Medical School, USA) for the Cre-conditional Sirt1 null mice; Kevin Williams (UTSW Medical Center, USA) for helping with electrophysiological studies; Joel Elmquist (UTSW Medical Center, USA) and Bradford Lowell (Harvard Medical School, USA) for critical reading of the manuscript; and Aktar Ali and Laura Brule for metabolic assessments at the Mouse Metabolic Phenotyping Core at UTSW Medical Center (supported by PL1 DK081182-01 and 1UL1RR024923-01). This work was supported by the Paul F. Glenn Foundation for Medical Research (D.A.S.); the American Heart Association (Scientist Development Grant to R.C. and Postdoctoral Fellowship to G.R.); by the Italian Ministry of Education, University, and Research (PRIN 2005 to R.C.); and by National Institutes of Health Grants (DK080836 to R.C., RL1DK081185 to E.D.B., AG028730 and AG027916 to D.A.S.). D.A.S. is a Senior Fellow of the Ellison Medical Foundation. ",
year = "2011",
month = sep,
day = "7",
doi = "10.1016/j.cmet.2011.06.014",
language = "English (US)",
volume = "14",
pages = "301--312",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}