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.