title: 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).
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.
authors.affiliation: From the Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland and.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Svensson
authors.affiliation: From the Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland and.
authors.forename: Svenia
authors.initials: S
authors.lastname: Schnyder
authors.affiliation: From the Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland and.
authors.forename: Verena
authors.initials: V
authors.lastname: Albert
authors.affiliation: From the Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland and.
authors.forename: Bettina
authors.initials: B
authors.lastname: Cardel
authors.affiliation: Department of Molecular Pathology, Institute for Pathology, University Hospital Basel, CH-4003 Basel, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Quagliata
authors.affiliation: Department of Molecular Pathology, Institute for Pathology, University Hospital Basel, CH-4003 Basel, Switzerland.
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Terracciano
authors.affiliation: From the Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland and christoph.handschin@unibas.ch.
authors.forename: Christoph
authors.identifier: http://orcid.org/0000-0003-0603-1097
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C525422:SRT1720; D013267:Stilbenes; D014157:Transcription Factors; D005947:Glucose; D000077185:Resveratrol
keywords: metabolic disease; metabolism; obesity; peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) (PPARGC1A); resveratrol; skeletal muscle