leptin and xanthohumol

We previously showed that xanthohumol-rich hop extract (XRHE, ~18% xanthohumol) exerts anti-obesity effects in rats fed a high-fat diet through regulation of fatty acid metabolism. In this study, we examined the effects of dietary purified xanthohumol from XRHE (PX, ~91.9% xanthohumol) in KK-Ay mice in order to understand the anti-obesity effects of xanthohumol alone because XRHE contains 82% unknown compounds. Dietary consumption of PX significantly inhibited an increase in the visceral fat weight of mice compared to those fed control diet without PX. Plasma leptin level was significantly lower in the PX-fed group than in the control group. Dietary PX lowered hepatic fatty acid synthesis by down-regulation of SREBP1c mRNA expression in the liver. On the other hand, fatty acid β-oxidation in the liver was promoted by dietary PX through the up-regulation of PPARα mRNA expression. Moreover, the fecal levels of fatty acids and carbohydrates increased by dietary PX. PX inhibited lipase or α-amylase activity in vitro. Thus, we found that PX may exert anti-obesity effects through the regulation of lipid metabolism and inhibition of intestinal fat and carbohydrate absorption, and that xanthohumol alone may exert anti-obesity effects.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Disease Models, Animal; Fasting; Fatty Acids; Flavonoids; Humulus; Intestinal Mucosa; Leptin; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred Strains; Obesity; Plant Extracts; Propiophenones; Sterol Regulatory Element Binding Protein 1

Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice.

Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Cholesterol, LDL; Dietary Fats; Flavonoids; Humulus; Insulin; Interleukin-6; Leptin; Lipid Metabolism; Liver; Male; Mice; Obesity; Propiophenones; Proprotein Convertase 9