Allicin induces beige-like adipocytes via KLF15 signal cascade.

Under specific conditions, white adipose tissue (WAT) depots are readily converted to a brown-like state, which is associated with weight loss. However, whether diet-derived factors directly induce browning of white adipocytes has yet to be established. Thus, we investigated the effects of allicin, one of the major components of garlic, on brown-like adipocyte formation in inguinal WAT (iWAT), and prevention of obesity and related complications in animal models. Allicin significantly increased mRNA and/or protein expression of brown adipocyte markers including uncoupling protein 1 (UCP1) in differentiated mouse embryonic fibroblast cell line 3T3-L1 and differentiated iWAT stromal vascular cells (SVC), suggesting that allicin induced brown-like adipocyte formation in vitro. Concomitantly, allicin markedly enhanced the protein expression of KLF-15 and its interaction with UCP-1 promoter region. Such changes were absent in cells lacking KLF-15, suggesting the critical role of KLF15 in allicin action. Allicin also induced brown-like adipogenesis in vivo along with the appearance of multilocular adipocytes, increased UCP1 expression and increased lipid oxidation. In summary, our data suggest that allicin potentially prevents obesity and associated metabolic disorders such as type 2 diabetes mellitus by enhancing the expression of brown adipocyte-specific genes, including UCP-1, through KLF15 signal cascade.