Isohumulones modulate blood lipid status through the activation of PPAR alpha.
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.
Shimura
Masako
M
Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., Yokohama 236-0004, Japan.
Hasumi
Akiko
A
Minato
Toshiko
T
Hosono
Mayu
M
Miura
Yutaka
Y
Mizutani
Satoru
S
Kondo
Keiji
K
Oikawa
Shinichi
S
Yoshida
Aruto
A
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
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