Sesamol promotes browning of white adipocytes through liver-adipose crosstalk signal of hepatic fibroblast growth factor 21

Abstract

Sesamol (SEM), a lignan from sesame oil, exhibited potential benefits on obesity treatment by promoting browning of adipocytes, and the current study is aimed to explore the molecular mechanisms of SEM from the aspect of systemic liver-adipose crosstalk that mediated by hepatic fibroblast growth factor 21 (FGF21). Our in vivo data showed that SEM induced energy expenditure and white adipose tissue (WAT) browning by increasing the expression level of uncoupling protein-1 in high fat diet induced obese C57BL/6J mice. Elevated levels of circulating FGF21 associated with the increased expression of hepatic FGF21 were observed after SEM intervention. Simultaneously, the increased adipose fibroblast growth factor tyrosine kinase receptor 1/beta-klotho indicated that FGF21 sensitivity was enhanced by SEM in WAT. Furthermore, our in vitro results from HepG2 and 3T3-L1 cell lines confirmed the effects and revealed the mechanism of SEM on the white adipocytes browning. We found that with the specific inhibitors of PPARα, the SEM-mediated hepatic FGF21 expression was decreased, and with the specific inhibitors of PPARγ, the browning effect of adipocytes by SEM combining with FGF21 was significantly suppressed. Taken together, the mechanism of SEM for inducing the WAT browning might be the modulation of SEM on liver-adipose crosstalk mediated by FGF21, and the PPARs family might be the targets of SEM. The novel findings from the present study provided evidence that SEM could be a potent obesity-treating compound.

Keywords: Crosstalk; FGF21; PPARα; PPARγ; Sesamol.