title: Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.
abstract: 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.
authors.affiliation: Linus Pauling Institute and Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Cristobal L
authors.initials: CL
authors.lastname: Miranda
authors.affiliation: Linus Pauling Institute and Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Valerie D
authors.initials: VD
authors.lastname: Elias
authors.affiliation: Linus Pauling Institute and Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Hay
authors.affiliation: Linus Pauling Institute and Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Choi
authors.affiliation: Linus Pauling Institute and Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Reed
authors.affiliation: Linus Pauling Institute and Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA. Electronic address: fred.stevens@oregonstate.edu.
authors.forename: Jan F
authors.initials: JF
authors.lastname: Stevens
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D027582:Humulus / Q000737:chemistry; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood* / Q000139:chemically induced; D011427:Propiophenones / Q000737:chemistry / Q000494:pharmacology*; D000071449:Proprotein Convertase 9 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D008078:Cholesterol, LDL; D004041:Dietary Fats; D005419:Flavonoids; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D011427:Propiophenones; C577686:interleukin-6, mouse; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; C104536:xanthohumol
keywords: C57BL/6J mice; Lipidomics; Metabolic syndrome; Obesity; PCSK9; Xanthohumol