Abstract
This review describes recent advances in our knowledge of the regulatory interactions influencing the expression of peroxisome proliferator-activated receptor (PPAR)-regulated genes. We address recent advances highlighting the role of PPARgamma (PPARG) coactivator-1 (PGC-1) and lipin-1 in co-ordinating the expression of genes controlling nutrient handling. We evaluate the possibility that SIRT1 lies at the heart of a regulatory loop involving PPARalpha, PGC-1alpha (PPARA, PPARGC1A as given in the HUGO Database), and lipin-1 (LPIN1 as listed in the HUGO Database) that ultimately controls the metabolic response to varying nutrient and physiological signals via a common mechanism mediated by post-translation modifications (deacetylation) of both PPARalpha and PGC-1s. Finally, we comment on the potential of pharmaceutical manipulation of these targets as well as the possible problems associated with this strategy.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adipose Tissue / metabolism
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Animals
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Heat-Shock Proteins / metabolism
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Humans
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Insulin / metabolism
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Lipid Metabolism
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Liver / metabolism
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Liver X Receptors
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Nuclear Proteins / metabolism*
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Orphan Nuclear Receptors / metabolism
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Peroxisome Proliferator-Activated Receptors / metabolism*
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Phosphatidate Phosphatase
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Protein Modification, Translational*
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Sirtuin 1 / metabolism*
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Transcription Factors / metabolism*
Substances
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Heat-Shock Proteins
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Insulin
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Liver X Receptors
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Nuclear Proteins
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Orphan Nuclear Receptors
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PPARGC1A protein, human
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Peroxisome Proliferator-Activated Receptors
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Transcription Factors
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peroxisome-proliferator-activated receptor-gamma coactivator-1
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LPIN1 protein, human
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Phosphatidate Phosphatase
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Sirtuin 1