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Resveratrol and SRT1720 elicit differential effects in metabolic organs and modulate systemic parameters independently of skeletal muscle peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)

Svensson, Kristoffer and Schnyder, Svenia and Albert, Verena and Cardel, Bettina and Quagliata, Luca and Terracciano, Luigi M. and Handschin, Christoph. (2015) Resveratrol and SRT1720 elicit differential effects in metabolic organs and modulate systemic parameters independently of skeletal muscle peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α). Journal of biological chemistry, 290 (26). pp. 16059-16076.

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Official URL: http://edoc.unibas.ch/dok/A6411086

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Abstract

Resveratrol (RSV) and SRT1720 (SRT) elicit beneficial metabolic effects and are postulated to ameliorate obesity and related metabolic complications. The co-activator, peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), has emerged as a major downstream effector responsible for metabolic remodeling of muscle and other metabolic tissues in response to RSV or SRT treatment. However, the requirement of PGC-1α in skeletal muscle for the systemic metabolic effects of these compounds has so far not been demonstrated. Using muscle-specific PGC-1α knock-out mice, we show that PGC-1α is necessary for transcriptional induction of mitochondrial genes in muscle with both RSV and SRT treatment. Surprisingly, the beneficial effects of SRT on glucose homeostasis and of both compounds on energy expenditure occur even in the absence of muscle PGC-1α. Moreover, RSV and SRT treatment elicit differential transcriptional effects on genes involved in lipid metabolism and mitochondrial biogenesis in liver and adipose tissue. These findings indicate that RSV and SRT do not induce analogous metabolic effects in vivo. Our results provide important insights into the mechanism, effects, and organ specificity of the caloric restriction mimetics RSV and SRT. These findings are important for the design of future therapeutic interventions aimed at ameliorating obesity and obesity-related metabolic dysfunction.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
UniBasel Contributors:Handschin, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Biological Chemists
ISSN:0021-9258
Note:This research was originally published in Journal of Biological Chemistry. 2015 © the American Society for Biochemistry and Molecular Biology -- Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:27 Sep 2017 09:54
Deposited On:07 Aug 2015 12:06

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