Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans

• Published in: Cell metabolism Vol. 14; no. 5; pp. 612 - 622
• Main Authors: Timmers, Silvie, Konings, Ellen, Bilet, Lena, Houtkooper, Riekelt H., van de Weijer, Tineke, Goossens, Gijs H., Hoeks, Joris, van der Krieken, Sophie, Ryu, Dongryeol, Kersten, Sander, Moonen-Kornips, Esther, Hesselink, Matthijs K.C., Kunz, Iris, Schrauwen-Hinderling, Vera B., Blaak, Ellen E., Auwerx, Johan, Schrauwen, Patrick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.11.2011
• Subjects: adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; alanine transaminase; Alanine Transaminase - analysis; AMP-Activated Protein Kinase Kinases; animal models; beta-cell function; Blood Glucose - analysis; Blood Pressure; Caloric Restriction - methods; citrate (si)-synthase; Citrate (si)-Synthase - biosynthesis; Cross-Over Studies; Double-Blind Method; energy metabolism; Energy Metabolism - drug effects; exercise; fat oxidation; fatty acids; Fatty Acids - metabolism; glucose; glycerol; Glycerol - blood; Heat-Shock Proteins - biosynthesis; Humans; inflammation; insulin sensitivity; life-span; lipid content; lipid-metabolism; lipolysis; Liver - drug effects; Liver - metabolism; low calorie diet; Male; men; Middle Aged; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - metabolism; mitochondrial-function; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; muscles; Netherlands; obesity; Obesity - drug therapy; Obesity - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; placebos; postprandial state; Protein Kinases - biosynthesis; resting metabolic rate; Resveratrol; saccharomyces-cerevisiae; sirt1 activation; Sirtuin 1 - biosynthesis; skeletal-muscle; Stilbenes - administration & dosage; Stilbenes - therapeutic use; Switzerland; systolic blood pressure; Transcription Factors - biosynthesis; triacylglycerols; Triglycerides - blood; Switzerland; Netherlands
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2011.10.002

Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. ► Resveratrol reduced sleeping metabolic rate in human, mimicking calorie restriction ► Resveratrol improved mitochondrial metabolism through the AMPK-SIRT1-PGC-1α axis ► Resveratrol decreased hepatic and increased muscle lipid content ► Resveratrol reduced inflammation markers in plasma and muscle