Carnosic acid and rosemary extract reversed the lipid accumulation induced by bisphenol A in the 3T3-L1 preadipocytes and C57BL/6J mice via SIRT1/FoxO1 pathway.

Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used to produce polycarbonate plastic. Carnosic acid (CA) is a rosemary diterpene with an anti-obesity effect. In this study, we investigated the anti-adipogenic effect of CA in BPA-treated 3T3-L1 preadipocytes and C57BL/6 J mice. In vitro experiments showed that CA inhibited lipid accumulation by BPA in 3T3-L1 preadipocytes. CA displayed anti-adipogenic effects through the downregulation of differentiation and adipogenesis-related proteins, along with the upregulation of lipolytic protein and SIRT1/FoxO1 pathway. In vivo experiments, mice treated with BPA exhibited an increase in body weight gain and epididymal adipose tissue mass when compared to the control group. CA treatment improved the epididymal adipose tissue mass induced by BPA. CA and rosemary extract (RE) treatment ameliorated dyslipidemia in BPA-treated mice. We further showed that CA and RE exerted anti-adipogenesis effects in liver tissues of BPA-treated mice via increasing SIRT1, FoxO1, and ATGL proteins and decreasing FAS and aP2 proteins. Moreover, SIRT1 inhibitor sirtinol blocked CA to increase SIRT1, FoxO1, FAS, and aP2 proteins, decrease Ac-FoxO1 protein, and reduce lipid accumulation in BPA-treated cells. These findings indicated that CA and RE could reverse BPA-induced lipid accumulation by regulating adipocyte differentiation, adipogenesis, and lipolysis through SIRT1/FoxO1 pathway.