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.
authors: Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Giorgio
authors: G
authors: Ramadori
authors: Teppei
authors: T
authors: Fujikawa
authors: Jason
authors: J
authors: Anderson
authors: Eric D
authors: ED
authors: Berglund
authors: Renata
authors: R
authors: Frazao
authors: Shaday
authors: S
authors: Michán
authors: Claudia R
authors: CR
authors: Vianna
authors: David A
authors: DA
authors: Sinclair
authors: Carol F
authors: CF
authors: Elias
authors: Roberto
authors: R
authors: Coppari
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000068797:Orexins; D018408:Patch-Clamp Techniques; D056564:Sirtuin 1 / Q000172:deficiency* / Q000235:genetics; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009479:Neuropeptides; D000068797:Orexins; D054339:Steroidogenic Factor 1; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1