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.
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ramadori
authors.forename: Teppei
authors.initials: T
authors.lastname: Fujikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuda
authors.forename: Jason
authors.initials: J
authors.lastname: Anderson
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.forename: Raul
authors.initials: R
authors.lastname: Mostoslavsky
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Stuart
authors.forename: Mario
authors.initials: M
authors.lastname: Perello
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Vianna
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Nillni
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppari
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism; D005260:Female; D006706:Homeostasis; D020738:Leptin / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D009765:Obesity / Q000209:etiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D020738:Leptin; D011333:Pro-Opiomelanocortin; D019869:Phosphatidylinositol 3-Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1