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.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea.
Youngwoo
Y
Song
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea.
Mi-Bo
MB
Kim
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea.
Changhee
C
Kim
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea.
Jongwook
J
Kim
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University , Seoul, Korea.
Jae-Kwan
JK
Hwang
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D019440:Anti-Obesity Agents; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage*; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000517:prevention & control; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D019440:Anti-Obesity Agents; D005419:Flavonoids; D014157:Transcription Factors; D014280:Triglycerides; C060298:5,7-dimethoxyflavone; D055372:AMP-Activated Protein Kinases
3T3-L1 adipocytes; 5,7-dimethoxyflavone; C57BL/6J mice; adipogenesis; obesity