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Increasing cAMP levels of preadipocytes by cyanidin-3-glucoside treatment induces the formation of beige phenotypes in 3T3-L1 adipocytes
Institution:1. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki, 305-8572, Japan;2. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba City, Ibaraki, 305-8572, Japan;3. Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba City, Ibaraki, 305-8572, Japan;1. Department of Microbiology and Immunology, Teikyo University School of Medicine, Tokyo, Japan;2. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan;3. Integrated Institute for Regulatory Science, Research Organization for Nano and Life Innovation, Waseda University, Tokyo, Japan;1. Laboratorio de Fisiopatología Cardiovascular, Instituto de Medicina y Biología Experimental de Cuyo, National Scientific and Technical Research Council (CONICET)-Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina;2. Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research “Alfredo Lanari,” Buenos Aires University and CONICET, Buenos Aires, Argentina;3. Laboratorio de Bioquímica Vegetal, Instituto de Biología Agrícola de Mendoza, CONICET-Universidad Nacional de Cuyo, M5528AHB, Mendoza, Argentina;4. Department of Nutrition and Department of Environmental Toxicology, University of California, Davis, CA, USA
Abstract:Obesity is a serious health problem and a major risk factor for the onset of several diseases such as heart disease, diabetes, stroke and cancer. The conversion of white adipocytes to brown-like adipocytes, also called beige or brite adipocytes, by pharmacological and dietary compounds has gained attention as an effective treatment for obesity. Cyanidin-3-glucoside (Cy3G), a polyphenolic compound contained in black soybean, blueberry and grape, has several antiobesity effects. However, there are no reports on the role of Cy3G in the induction of differentiation of preadipocytes to beige adipocytes and corresponding phenotypes. Here, the formation of beige adipocyte phenotypes following treatment with Cy3G was evaluated using 3T3-L1 adipocytes. Cy3G induced phenotypic changes to white adipocytes, such as increased multilocular lipid droplets and mitochondrial content. Additionally, the expression of mitochondrial genes (TFAM, SOD2, UCP-1 and UCP-2), UCP-1 protein and beige adipocyte markers (CITED1 and TBX1) in 3T3-L1 adipocytes was increased by Cy3G. Furthermore, Cy3G promoted preadipocyte differentiation by up-regulating of C/EBPβ through the elevation of the intracellular cAMP levels. These results indicated that Cy3G elevates the intracellular cAMP levels, which induces beige adipocyte phenotypes. This is the first report on the effect of Cy3G on induction of differentiation of preadipocytes into beige adipocyte phenotypes.
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