Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of ligand-activated nuclear transcription factors. Three PPAR subtypes, PPARα, PPARδ (PPARβ) and PPARγ, have been described in mammals. The tissue distribution of PPARs is heterogeneous: PPARα is highly expressed in liver and skeletal muscle, PPARγ is preferentially expressed in adipose tissues, and PPARδ is expressed in most cell types with relative abundance. Unlike most receptors, PPARs show low ligand specificity, being activated by many long-chain saturated and unsaturated fatty acids, or by eicosanoids. PPARs are transcriptionally active as heterodimeric complexes with the retinoid X receptor and bind to specific recognition sequences in the regulatory region of target genes. Many PPAR-regulated genes encode proteins that regulate fatty acid oxidation and storage. Elucidation of the biological functions of PPARs has been aided by the development of PPAR-null mice and the identification of humans bearing PPAR mutations, together with the discovery of synthetic small-molecule ligands that selectively activate individual PPAR subtypes. Using these genetic and pharmacological approaches, it has been shown that PPARα predominantly regulates pathways of fatty acid oxidation, whereas PPARγ modifies fatty acid synthesis and storage in adipose tissues. By reducing systemic fatty acid availability, thiazolidinedione PPARγ activators regulate glucose metabolism and are now used clinically in the treatment of Type II diabetes. In summary, PPARs play a central role in the mechanisms that balance fatty acid oxidation and storage in the face of fluctuations of dietary fat intake and energy expenditure.
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November 2002
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Conference Article|
November 01 2002
Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism
S. A. Smith
S. A. Smith
1
1Metabolic Scientific Strategy, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, U.K.
1E-mail stephen_a_smith@gsk.com
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Publisher: Portland Press Ltd
Received:
June 11 2002
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (6): 1086–1090.
Article history
Received:
June 11 2002
Citation
S. A. Smith; Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism. Biochem Soc Trans 1 November 2002; 30 (6): 1086–1090. doi: https://doi.org/10.1042/bst0301086
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