Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M403456200 on June 3, 2004

J. Biol. Chem., Vol. 279, Issue 32, 33456-33462, August 6, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
279/32/33456    most recent
M403456200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yajima, H.
Right arrow Articles by Kondo, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yajima, H.
Right arrow Articles by Kondo, K.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Isohumulones, Bitter Acids Derived from Hops, Activate Both Peroxisome Proliferator-activated Receptor {alpha} and {gamma} and Reduce Insulin Resistance*

Hiroaki Yajima{ddagger}§, Emiko Ikeshima{ddagger}, Maho Shiraki{ddagger}, Tomoka Kanaya{ddagger}, Daisuke Fujiwara{ddagger}, Hideharu Odai{ddagger}, Nobuyo Tsuboyama-Kasaoka¶, Osamu Ezaki¶, Shinichi Oikawa||, and Keiji Kondo{ddagger}

From the {ddagger}Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., Kanagawa 236-0004, Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo 162-8636, and the ||Department of Medicine, Nippon Medical School, Tokyo 113-8603, Japan

The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of fibrate drugs and the therapeutic benefits of the thiazolidinedione drugs are due to their activation of PPAR{alpha} and -{gamma}, respectively. In this study, isohumulones, the bitter compounds derived from hops that are present in beer, were found to activate PPAR{alpha} and -{gamma} in transient co-transfection studies. Among the three major isohumulone homologs, isohumulone and isocohumulone were found to activate PPAR{alpha} and -{gamma}. Diabetic KK-Ay mice that were treated with isohumulones (isohumulone and isocohumulone) showed reduced plasma glucose, triglyceride, and free fatty acid levels (65.3, 62.6, and 73.1%, respectively, for isohumulone); similar reductions were found following treatment with the thiazolidinedione drug, pioglitazone. Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10.6% increase versus control group). C57BL/6N mice fed a high fat diet that were treated with isohumulones showed improved glucose tolerance and reduced insulin resistance. Furthermore, these animals showed increased liver fatty acid oxidation and a decrease in size and an increase in apoptosis of their hypertrophic adipocytes. A double-blind, placebo-controlled pilot study for studying the effect of isohumulones on diabetes suggested that isohumulones significantly decreased blood glucose and hemoglobin A1c levels after 8 weeks (by 10.1 and 6.4%, respectively, versus week 0). These results suggest that isohumulones can improve insulin sensitivity in high fat diet-fed mice with insulin resistance and in patients with type 2 diabetes.


Received for publication, March 29, 2004 , and in revised form, May 26, 2004.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Central Laboratories for Key Technology, Kirin Brewery Co., Ltd., 1-13-5, Fukuura Kanazawa-ku Yokohama, Kanagawa 236-0004, Japan. Tel.: 81-45-788-7244; Fax: 81-45-788-4042; E-mail: hyajima{at}kirin.co.jp.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Drug Metab. Dispos.Home page
L. Wang, D. Zhang, A. Swaminathan, Y. Xue, P. T. Cheng, S. Wu, R. Mosqueda-Garcia, C. Aurang, D. W. Everett, and W. G. Humphreys
GLUCURONIDATION AS A MAJOR METABOLIC CLEARANCE PATHWAY OF 14C-LABELED MURAGLITAZAR IN HUMANS: METABOLIC PROFILES IN SUBJECTS WITH OR WITHOUT BILE COLLECTION
Drug Metab. Dispos., March 1, 2006; 34(3): 427 - 439.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement