Preserved glucose tolerance in high-fat-fed C57BL/6 mice transplanted with PPARγ−/−, PPARδ−/−, PPARγδ−/−, or LXRαβ−/− bone marrow
| Autor: | Chaitra Marathe, Michelle N. Bradley, Cynthia Hong, Lily Chao, Damien Wilpitz, Jon Salazar, Peter Tontonoz |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Journal of Lipid Research, Vol 50, Iss 2, Pp 214-224 (2009) |
| Druh dokumentu: | article |
| ISSN: | 0022-2275 25472186 |
| DOI: | 10.1194/jlr.M800189-JLR200 |
| Popis: | 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 PPARγ−/−, PPARδ−/−, PPARγδ−/−, and LXRαβ−/− 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 PPARγ, suggesting that cell types other than macrophages are the primary mediators of the anti-diabetic effects of PPARγ 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. |
| Databáze: | Directory of Open Access Journals |
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