No abstract

We have previously reported that Muscadine grape polyphenols (MGP) reduced high fat diet‐mediated visceral obesity in vivo. However, underlying mechanisms by which MGP reverses visceral obesity is unknown. The aim of this study was to determine the novel inhibitory roles of MGP on hypertrophic (increase in size) or hyperplastic (new fat cell formation) obesity. Consistent with reduced fat mass, epididymal adipocyte size was significantly smaller in MGP group compared to the HF‐control, suggesting that MGP reduces hypertrophic obesity. We also investigated the effects of MGP on adipogenesis using human adipose‐derived stem cells (hASCs). After fractionating MGP into anthocyanin and non‐anthocyanin fractions, only the non‐anthocyanin fraction inhibited adipogenic conversion of hASCs in a dose‐dependent manner. Among the non‐anthocyanidin polyphenols, ellagic acid has been identified as the responsible polyphenol that exclusively represses the adipogenesis. Ellagic acid repressed adipogenesis by blocking the obligatory reduction of histone deacetylase (HDAC) activity for adipogenic gene transcription. Both TSA‐sensitive and ‐ insensitive HDAC activities were modified by ellagic acid with selective increases of HADAC 1, 2 and 4, but not HADC3. Collectively, these data suggest that ellagic acid attenuates hyperplastic conversion of hASCs via HDAC activity mediated‐epigenetic modification.Grant Funding Source: Florida Department of Agriculture and Consumer Service, Viticulture Research Program