Prevention of Obesity and Hyperlipidemia by Heptamethoxyflavone in High-fat Diet-induced Rats

Polymethoxyflavones (PMFs) have been shown to prevent obesity, ameliorate type 2 diabetes, and regulate lipid metabolism in vitro and in vivo. However, little is known about the contribution of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) to prevent obesity and regulate lipid metabolism in vivo. We aimed to investigate the potential efficacy of HMF on preventing obesity and hyperlipidemia in rats fed a high-fat diet (HFD) and its underlying mechanisms. Male Sprague-Dawley rats were fed a normal diet or an HFD with or without HMF (0.02%, 0.04% and 0.08%, w/w) for 6 weeks. The supplementation of HMF not only significantly decreased body weight gain (HFD, 336.50 +/- 18.84 g; LHMF, 309.43 +/- 20.74 g; MHMF, 296.83 +/- 13.88 g; HHMF, 265.71 +/- 19.09 g; respectively, p < 0.05) and adipose tissues weight (p < 0.05), but also markedly lowered serum levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol (p < 0.05) in the sixth week in a dose-dependent manner compared with the HFD group. HMF also significantly alleviated hepatic steatosis in the liver (liver weight g/100 g body weight of HFD, 4.86 +/- 0.11%; LHMF, 4.02 +/- 0.33%; MHMF, 4.05 +/- 0.31%; HHMF, 3.72 +/- 0.34%; respectively, p < 0.05). Furthermore, transcriptome analysis and real-time quantitative RT-PCR demonstrated that HMF supplementation markedly downregulated hepatic genes related to adipogenesis transcription and inflammatory responses, and significantly upregulated genes related to fatty acid oxidation and energy expenditure. These results indicated that HMF could effectively prevent obesity and hyperlipidemia by regulation of the expression of lipid metabolism-related and inflammatory response-related genes.