Acacetin alleviates energy metabolism disorder through promoting white fat browning mediated by AC-cAMP pathway

ABSTRACT

Acacetin (ACA), a flavone isolated from Chinese traditional medical herbs, has numerous pharmacological activities. However, little is known about the roles in white fat browning and energy metabolism. In the present study, we investigated whether and how ACA would improve energy metabolism in vivo and in vitro. ACA (20 mg/kg) was intraperitoneally injected to the mice with obesity induced by HFD for 14 consecutive days (in vivo); differentiated 3T3-L1 adipocytes were treated with ACA (20 µmol/L and 40 µmol/L) for 24 h (in vitro). The metabolic profile, lipid accumulation, fat-browning and mitochondrial contents, and so on were respectively detected. The results in vivo showed that ACA significantly reduced the body weight and visceral adipose tissue weight, alleviated the energy metabolism disorder, and enhanced the browning-related protein expressions in adipose tissue of rats. Besides, the data in vitro revealed that ACA significantly reduced the lipid accumulation, induced the expressions of the browning-related proteins and cAMP-dependent protein kinase A (PKA), and increased the mitochondrium contents, especially enhanced the energy metabolism of adipocytes; however, treatment with beta-adrenergic receptor blocker (propranolol, Pro) or adenyl cyclase (AC) inhibitor (SQ22536, SQ) abrogated the ACA-mediated effects. The data demonstrate that ACA alleviates the energy metabolism disorder through the pro-browning effects mediated by the AC-cAMP pathway. The findings would provide the experimental foundation for ACA to prevent and treat obesity and related metabolism disorders. (AU)