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Celastrol Protects against Obesity and Metabolic Dysfunction through Activation of a HSF1-PGC1alpha Transcriptional Axis.

Authors: Ma, X  Xu, L  Alberobello, AT  Gavrilova, O  Bagattin, A  Skarulis, M  Liu, J  Finkel, T  Mueller, E 
Citation: Ma X, etal., Cell Metab. 2015 Oct 6;22(4):695-708. doi: 10.1016/j.cmet.2015.08.005. Epub 2015 Sep 3.
Pubmed: (View Article at PubMed) PMID:26344102
DOI: Full-text: DOI:10.1016/j.cmet.2015.08.005

Altering the balance between energy intake and expenditure is a potential strategy for treating obesity and metabolic syndrome. Nonetheless, despite years of progress in identifying diverse molecular targets, biological-based therapies are limited. Here we demonstrate that heat shock factor 1 (HSF1) regulates energy expenditure through activation of a PGC1alpha-dependent metabolic program in adipose tissues and muscle. Genetic modulation of HSF1 levels altered white fat remodeling and thermogenesis, and pharmacological activation of HSF1 via celastrol was associated with enhanced energy expenditure, increased mitochondrial function in fat and muscle and protection against obesity, insulin resistance, and hepatic steatosis during high-fat diet regimens. The beneficial metabolic changes elicited by celastrol were abrogated in HSF1 knockout mice. Overall, our findings identify the temperature sensor HSF1 as a regulator of energy metabolism and demonstrate that augmenting HSF1 via celastrol represents a possible therapeutic strategy to treat obesity and its myriad metabolic consequences.

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RGD Object Information
RGD ID: 11522116
Created: 2016-08-03
Species: All species
Last Modified: 2016-08-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.