ECE2017 Eposter Presentations: Interdisciplinary Endocrinology Cardiovascular Endocrinology and Lipid Metabolism (9 abstracts)
1Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca (VHIR), Barcelona, Spain; 2Research Group on Neuromuscular and Mitochondrial Diseases, Vall Hebron Institut de Recerca (VHIR), Barcelona, Spain; 3Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Sex hormone-binding globulin (SHBG) carries sex steroids in blood regulating their bioavailability. Red wine consumption increases plasma SHBG levels, and we have discovered that resveratrol, a polyphenol enriched in red wine, acts specifically through the human constitutive androstane receptor (CAR), a drug/xenobiotic detoxification gene regulator, to increase hepatic SHBG production. Chromatin immunoprecipitation and luciferase reporter gene assays show that human CAR binds to a typical direct repeat 1 nuclear hormone receptor-binding element in the human SHBG proximal promoter. Resveratrol also increased hepatic SHBG production in humanized SHBG/CAR transgenic mice. Moreover, SHBG expression correlated significantly with CAR mRNA levels in human liver biopsies. We conclude that the beneficial effects of red wine on the metabolic syndrome and it associated co-morbidities, including cardiovascular disease and type 2 diabetes, may be mediated in part by resveratrol acting via CAR to increase plasma SHBG levels.