title: Comprehensive Metabolomic Analysis in Blood, Urine, Fat, and Muscle in Men with Metabolic Syndrome: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Resveratrol after Four Months' Treatment.
abstract: Resveratrol possesses several beneficial metabolic effects in rodents, while the effects of resveratrol in humans remain unclear. Therefore, we performed a non-targeted comprehensive metabolomic analysis on blood, urine, adipose tissue, and skeletal muscle tissue in middle-aged men with metabolic syndrome randomized to either resveratrol or placebo treatment for four months. Changes in steroid hormones across all four matrices were the most pronounced changes observed. Resveratrol treatment reduced sulfated androgen precursors in blood, adipose tissue, and muscle tissue, and increased these metabolites in urine. Furthermore, markers of muscle turnover were increased and lipid metabolism was affected, with increased intracellular glycerol and accumulation of long-chain saturated, monounsaturated, and polyunsaturated (n3 and n6) free fatty acids in resveratrol-treated men. Finally, urinary derivatives of aromatic amino acids, which mainly reflect the composition of the gut microbiota, were altered upon resveratrol treatment. In conclusion, the non-targeted metabolomics approach applied to four different matrices provided evidence of subtle but robust effects on several metabolic pathways following resveratrol treatment for four months in men with metabolic syndrome-effects that, for the most part, would not have been detected by routine analyses. The affected pathways should be the focus of future clinical trials on resveratrol's effects, and perhaps particularly the areas of steroid metabolism and the gut microbiome.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Institute of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark. korsholm@clin.au.dk.
authors.forename: Anne Sofie
authors.initials: AS
authors.lastname: Korsholm
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Institute of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark. thomas.kjaer@clin.au.dk.
authors.forename: Thomas Nordstrøm
authors.initials: TN
authors.lastname: Kjær
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Institute of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark. Marie.juul.ornstrup@clin.au.dk.
authors.forename: Marie Juul
authors.initials: MJ
authors.lastname: Ornstrup
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Institute of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark. amtssp@gmail.com.
authors.forename: Steen Bønløkke
authors.initials: SB
authors.lastname: Pedersen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D015415:Biomarkers; D001794:Blood Pressure; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D013267:Stilbenes; D000077185:Resveratrol
keywords: gut microbiome; inflammation; insulin sensitivity; metabolic syndrome; metabolite profiling; metabolomics; natural bioactive agents; obesity; resveratrol