@article{50a5e62bd55b413a99948421e4e33e40,
title = "SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity",
abstract = "Feeding on high-calorie (HC) diets induces serious metabolic imbalances, including obesity. Understanding the mechanisms against excessive body weight gain is critical for developing effective antiobesity strategies. Here we show that lack of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase SIRT1 in pro-opiomelanocortin (POMC) neurons causes hypersensitivity to diet-induced obesity due to reduced energy expenditure. The ability of leptin to properly engage the phosphoinositide 3-kinase (PI3K) signaling in POMC neurons and elicit remodeling of perigonadal white adipose tissue (WAT) is severely compromised in mutant mice. Also, electrophysiological and histomorphomolecular analyses indicate a selective reduction in sympathetic nerve activity and brown-fat-like characteristics in perigonadal WAT of mutant mice, suggesting a physiologically important role for POMC neurons in controlling this visceral fat depot. In summary, our results provide direct genetic evidence that SIRT1 in POMC neurons is required for normal autonomic adaptations against diet-induced obesity.",
keywords = "HUMDISEASE, MOLNEURO",
author = "Giorgio Ramadori and Teppei Fujikawa and Makoto Fukuda and Jason Anderson and Morgan, {Donald A.} and Raul Mostoslavsky and Stuart, {Ronald C.} and Mario Perello and Vianna, {Claudia R.} and Nillni, {Eduardo A.} and Kamal Rahmouni and Roberto Coppari",
note = "Funding Information: We thank Wenhao Li and Kristen Wertz for technical assistance, Dr. Joyce Repa (UTSW Medical Center, USA) for quantitative real-time PCR primers, Dr. Yoshiyuki Horio (Sapporo Medical School, Japan) for the SIRT1 antisera, Dr. Frederick Alt (Harvard Medical School, USA) for the Cre-conditional Sirt1 null mice, Dr. 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), and Drs. Joel K. Elmquist (UTSW Medical Center, USA) and Bradford B. Lowell (Harvard Medical School, USA) for helpful discussions and careful reading of the manuscript. This work was supported by the Department of Internal Medicine/Division of Hypothalamic Research, UTSW Medical Center (start-up to R.C.), the American Heart Association (Scientist Development Grant to R.C. and Postdoctoral Fellowship to G.R.), and by National Institute of Health Grants (DK080836 to R.C. and DK58148 to E.A.N.). ",
year = "2010",
month = jul,
day = "7",
doi = "10.1016/j.cmet.2010.05.010",
language = "English (US)",
volume = "12",
pages = "78--87",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}