HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Free via Author's Choice: AC AC Full Text Full Text (PDF) AC All Versions of this Article: M800189-JLR200v1 50/2/214    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Marathe, C. Articles by Tontonoz, P. Search for Related Content PubMed PubMed Citation Articles by Marathe, C. Articles by Tontonoz, P. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 214-224, February 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Preserved glucose tolerance in high-fat-fed C57BL/6 mice transplanted with PPAR^–/–, PPAR^–/–, PPAR^–/–, or LXRβ^–/– bone marrow^*

Chaitra Marathe, Michelle N. Bradley, Cynthia Hong, Lily Chao, Damien Wilpitz, Jon Salazar and Peter Tontonoz¹

Howard Hughes Medical Institute, Molecular Biology Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095

^* This work was supported by National Institutes of Health grant HL030568.

Published, JLR Papers in Press, September 4, 2008.

¹ To whom correspondence should be addressed. e-mail: ptontonoz{at}mednet.ucla.edu

Macrophage lipid metabolism and inflammatory responses are both regulated by the nuclear receptors PPAR and LXR. Emerging links between inflammation and metabolic disease progression suggest that PPAR and LXR signaling may alter macrophage function and thereby impact systemic metabolism. In this study, the function of macrophage PPAR and LXR in Th1-biased C57BL/6 mice was tested using a bone marrow transplantation approach with PPAR^–/–, PPAR^–/–, PPAR^–/–, and LXRβ^–/– cells. Despite their inhibitory effects on inflammatory gene expression, loss of PPARs or LXRs in macrophages did not exert major effects on obesity or glucose tolerance induced by a high-fat diet. Treatment with rosiglitazone effectively improved glucose tolerance in mice lacking macrophage PPAR, suggesting that cell types other than macrophages are the primary mediators of the anti-diabetic effects of PPAR agonists in our model system. C57BL/6 macrophages lacking PPARs or LXRs exhibited normal expression of most alternative activation gene markers, indicating that macrophage alternative activation is not absolutely dependent on these receptors in the C57BL/6 background under the conditions used here. These studies suggest that genetic background may be an important modifier of nuclear receptor effects in macrophages. Our results do not exclude a contribution of macrophage PPAR and LXR expression to systemic metabolism in certain contexts, but these factors do not appear to be dominant contributors to glucose tolerance in a high-fat-fed Th1-biased bone marrow transplant model.

Supplementary key words PPAR • LXR • macrophage • inflammation • insulin resistance • immune phenotype

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