Non-alcoholic fatty liver disease (
NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with
NAFLD is rapidly increasing because of the
obesity epidemic. There are currently no approved drugs that prevent or treat
NAFLD. Recent evidence shows that
bavachin, a
flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and
insulin sensitivity during preadipocyte differentiation, but the effect of
bavachin on
glucose and lipid metabolism remains unclear. In the current study we investigated the effects of
bavachin on
obesity-associated
NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with
bavachin (20 μM) significantly suppressed PA/OA or high
glucose/high
insulin-induced increases in the expression of
fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore,
bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3β, improving the
insulin signaling activity in the cells. In HFD-induced obese mice, administration of
bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in
body weight, liver weight,
blood glucose, and liver and serum
triglyceride contents. Moreover,
bavachin administration significantly alleviated hepatic
inflammation and ameliorated HFD-induced
glucose intolerance and
insulin resistance. We demonstrated that
bavachin protected against HFD-induced
obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that
bavachin repressed the expression of
lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion,
bavachin attenuates hepatic steatosis and
obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that
bavachin is a potential
drug for
NAFLD therapy.