Searching across hundreds of databases
In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of Sirt1 in the brain, particularly the hypothalamus, in body weight and energy balance regulation is debated. Among the first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague Dawley rats. In that study, central inhibition of Sirt1 decreased body weight and food intake as a result of a Forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which, in turn, increased phosphorylated FoxO1 via improved insulin/pAKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-MSH maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.
Pubmed ID: 24773342 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets DIO2
View all literature mentionsThis monoclonal targets Cpe
View all literature mentionsThis monoclonal targets FoxO1 (C29H4) Rabbit mAb
View all literature mentionsThis polyclonal targets Angiotensinase C (T-15)
View all literature mentionsThis polyclonal targets Foxo1
View all literature mentionsThis monoclonal targets
View all literature mentionsThis polyclonal targets Phospho-FoxO1 (Ser256)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473) (193H12) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-Stat3 (Tyr705) Antibody detects endogenous levels of Stat3 only when phosphorylated at Tyr705. The antibody does not cross-react with other Stat proteins when phosphorylated on the corresponding tyrosine residue. Does cross-react withPhospho-EGFR
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
