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Integration of metabolism and inflammation by lipid-activated nuclear receptors

Abstract

The nuclear receptors known as PPARs and LXRs are lipid-activated transcription factors that have emerged as key regulators of lipid metabolism and inflammation. PPARs and LXRs are activated by non-esterified fatty acids and cholesterol metabolites, respectively, and both exert positive and negative control over the expression of a range of metabolic and inflammatory genes. The ability of these nuclear receptors to integrate metabolic and inflammatory signalling makes them attractive targets for intervention in human metabolic diseases, such as atherosclerosis and type 2 diabetes, as well as for the modulation of inflammation and immune responses.

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Figure 1: A model for signal-specific PPAR-γ- and LXR-mediated transrepression.
Figure 2: Integration of lipid and cytokine signals by PPAR-γ and PGC1β.

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Acknowledgements

P.T. is an investigator of the Howard Hughes Medical Institute. Work in the authors' laboratories was supported by National Institutes of Health grants HL66088 and HL30568 (P.T.) and RR021975 (S.J.B.).

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Bensinger, S., Tontonoz, P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454, 470–477 (2008). https://doi.org/10.1038/nature07202

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