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PPARs and the complex journey to obesity

Nature Medicine volume 10, pages 355–361 (2004)Cite this article

Abstract

Obesity and the related disorders of dyslipidemia and diabetes (components of syndrome X) have become global health epidemics. Over the past decade, the elucidation of key regulators of energy balance and insulin signaling have revolutionized our understanding of fat and sugar metabolism and their intimate link. The three 'lipid-sensing' peroxisome proliferator–activated receptors (PPAR-α, PPAR-γ and PPAR-δ) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bona fide therapeutic targets. With molecular underpinnings now in place, new pharmacologic approaches to metabolic disease and new questions are emerging.

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Figure 1: Central controls of appetite and energy expenditure.
Figure 2: Tissue-tissue cross-talk in glucose and lipid homeostasis.
Figure 3: Metabolic integration by PPARs.

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Acknowledgements

We thank R. Yu and W. He for critical reading of this manuscript, J. Simon for graphic artwork, and L. Ong and E. Stevens for administrative assistance. R.M.E. is an Investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies, and March of Dimes Chair in Molecular and Developmental Biology. G.D.B. is supported by National Institutes of Health Public Health Services Grant CA09370-23. This work was supported by the Howard Hughes Medical Institute, the Hilblom Foundation and grant U19DK62434 from the National Institutes of Health Nuclear Receptor Signaling Atlas orphan receptor program. We apologize to our colleagues that many primary references could not be included because of space limitations.

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  1. Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, 92037, California, USA

    Ronald M Evans, Grant D Barish & Yong-Xu Wang

  2. Ronald M Evans, Grant D Barish & Yong-Xu Wang

  3. Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, San Francisco, 94121, California, USA

    Grant D Barish

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Evans, R., Barish, G. & Wang, YX. PPARs and the complex journey to obesity. Nat Med 10, 355–361 (2004). https://doi.org/10.1038/nm1025

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