Anti-Obesity Effects of Isohumulones by Modulating Lipoid Metabolism via Peroxisome Proliferator-Activated Receptors

Obesity, the abnormal excessive growth of adipose tissue and accumulation of abdominal fat, results from the combined effects of excess energy intake and reduced energy expenditure. Obesity raises the risk for cardiovascular disease (CVD). Isohumulones, which impart bitter flavor and an antibacterial property to beers, are generated from humulones in the female inflorescences of the hop plant (Humulus lupulus L.) during the brewing process. In this study, we examined the anti-obesity effect of isomerized hop extract (IHE), which consists mainly of isohumulones. Supplementation of a high-tat diet with IHE reduced body weight gain and improved glucose tolerance in C57BL/6N and KK-A(y) mice. IHE also significantly decreased blood triglyceride and free fatty acid levels in these mice, suggesting that IHE is effective in preventing obesity and lowering the risk for CVD. Quantitative real-time PCR indicated that IHE up-regulated the expression of hepatic genes involved in peroxisomal and mitochondrial beta-oxidation. These effects were very similar to those that follow administration of hypolipidemic drugs with the potential of activating the PPAR alpha, and were not seen in PPAR alpha-deficient mice. As well as IHE, purified isohumulone or isocohumulone clearly activated PPAR alpha and gamma in vitro and showed similar anti-diabetic and hypolipidemic effects in mice. Taken together, our results suggested that isohumulones may be potentially effective for the prevention of obesity, diabetes, and dyslipidemia in metabolic syndrome.