5,7-Dimethoxyflavone Attenuates Obesity by Inhibiting Adipogenesis in 3T3-L1 Adipocytes and High-Fat Diet-Induced Obese C57BL/6J Mice

The antiobesity effect of 5,7-dimethoxyflavone (DMF) was evaluated in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese C57BL/6J mice. The accumulation of lipid droplets and triglycerides in adipocytes was dose dependently suppressed by DMF through inhibition of adipogenesis. DMF downregulated the adipogenic transcription factors (Peroxisome Proliferator-activated Receptor [PPAR]γ, CCAAT/enhancer binding protein [C/EBP]α, and sterol regulatory element-binding protein-1c [SREBP-1c]) and lipid synthesis Enzymes (fatty acid synthase [FAS], Acetyl-CoA Carboxylase [ACC], lipoprotein Lipase [LPL], and HMG-CoA reductase [HMGR]). AMP-activated protein kinase (AMPK) and AMPK related lipolytic proteins in differentiated adipocytes were activated by DMF. In the animal model, oral administration of DMF (50 mg/kg/day for 6 weeks) significantly decreased body weight gain without affecting food intake. Elevated serum levels of total Cholesterol and low-density lipoprotein Cholesterol were suppressed by DMF. Fat pad masses were reduced in DMF-treated obese mice, as evidenced by reduced adipocyte size. DMF altered the expression of adipogenic transcription factors in epididymal fat tissue. In addition, DMF attenuated HFD-induced nonalcoholic fatty liver disease by decreasing hepatic triglyceride accumulation. Overall, these results suggest that DMF is a potential natural agent for attenuating obesity and other obesity-related metabolic syndromes.

3T3-L1 adipocytes; 5,7-dimethoxyflavone; C57BL/6J mice; adipogenesis; obesity.