PPAR control: it's SIRTainly as easy as PGC.
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.
Sugden
Mary C
MC
Centre for Diabetes, Queen Mary University of London, Blizard Institute of Cell and Molecular Science, St Bartholomew's and the Royal London School of Medicine and Dentistry, Whitechapel, London E1 2AT, UK. m.c.sugden@qmul.ac.uk
Caton
Paul W
PW
Holness
Mark J
MJ
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D009687:Nuclear Proteins / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010711:Phosphatidate Phosphatase; D046188:Protein Modification, Translational; D056564:Sirtuin 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D006360:Heat-Shock Proteins; D007328:Insulin; D000071518:Liver X Receptors; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C485999:LPIN1 protein, human; D010711:Phosphatidate Phosphatase; D056564:Sirtuin 1