title: Isohumulones modulate blood lipid status through the activation of PPAR alpha.
abstract: Isohumulones derived from hops are the major bitter compounds in beer. It was recently reported that isohumulones activated peroxisome proliferator-activated receptors (PPARs) alpha and gamma in vitro and modulated glucose and lipid metabolism in vivo. In this study, we examined the effects of isomerized hop extract (IHE) primarily containing isohumulones in C57BL/6N male mice and found that such treatment increased their liver weight and reduced their plasma triglyceride and free fatty acid levels. Microarray analysis and quantitative real time PCR (QPCR) showed that IHE dose-dependently upregulated the expression of a battery of hepatic genes that are involved in microsomal omega-oxidation and peroxisomal and mitochondrial beta-oxidation. These effects were common in both genders and very similar to those found with the PPARalpha agonist, fenofibrate (FF). Moreover, these effects were not found in PPARalpha-deficient mice. Thus, our results strongly suggest that IHE intake upregulates the expression of key genes that are involved in hepatic fatty acid oxidation, and that it ameliorates the blood lipid profile by activating PPARalpha.
authors.affiliation: Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., Yokohama 236-0004, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Shimura
authors.forename: Akiko
authors.initials: A
authors.lastname: Hasumi
authors.forename: Toshiko
authors.initials: T
authors.lastname: Minato
authors.forename: Mayu
authors.initials: M
authors.lastname: Hosono
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Satoru
authors.initials: S
authors.lastname: Mizutani
authors.forename: Keiji
authors.initials: K
authors.lastname: Kondo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
authors.forename: Aruto
authors.initials: A
authors.lastname: Yoshida
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D000818:Animals; D019748:Carbon-Carbon Double Bond Isomerases / Q000378:metabolism; D003517:Cyclopentanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019998:Racemases and Epimerases / Q000378:metabolism; D012737:Sex Factors
chemical_list: D003517:Cyclopentanes; D008055:Lipids; D047493:PPAR alpha; C038784:fatty acid oxidation complex; C081209:isohumulone; D015094:3-Hydroxyacyl CoA Dehydrogenases; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase; D019998:Racemases and Epimerases; D019748:Carbon-Carbon Double Bond Isomerases