Anthocyanin oligomers stimulate browning in 3T3-L1 white adipocytes via activation of the β3-adrenergic receptor and ERK signaling pathway

Microbial fermentation of grape-skin extracts is found to synthesize anthocyanin oligomers (AO), which are more active than the monomeric anthocyanins that are effective for some metabolic diseases such as diabetes and obesity. This study investigated the functional role of AO in 3T3-L1 white adipocyte metabolism, with a focus on inducing browning. To achieve this, we determined the expressions of core genes and protein markers responsible for browning and lipid metabolism in response to AO treatment of 3T3-L1 white adipocytes. AO exposure significantly increases the expressions of beige-specific genes (Cidea, Cited1, Ppargc1 alpha, Prdm16, Tbx1, Tmem26, and Ucp1) and brown-fat signature proteins (UCP1, PRDM16, and PGC-1 alpha), and suppresses the expressions of lipogenic marker proteins while enhancing the protein levels of lipolysis in white adipocytes. The mechanistic study revealed stimulation of white fat browning via activation of the beta 3-AR/PKA/p38 axis and ERK/CREB signaling pathway subsequent to AO treatment. In conclusion, our current findings indicate the beneficial effects of AO for the treatment of obesity with interesting properties such as regulating the browning of adipocytes and increasing thermogenic activity. Although further research based on animal models or clinical trials remains, AO treatment can bring more insights into the treatment of obesity and metabolic syndrome.