Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats.
The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-gamma coactivator1alpha (PGC-1alpha) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1alpha mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1alpha, while the transcription factor PPAR-gamma remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycerides (MCT), SIRT1 and PGC-1alpha mRNA were restored to near control levels. This study demonstrates that alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1alpha and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications.
Lieber
Charles S
CS
Section of Liver Diseases, James J. Peters VA Medical Center, 130 West Kingsbridge Road (151-2), Bronx, NY 10468, USA. liebercs@aol.com
Leo
Maria A
MA
Wang
Xiaolei
X
Decarli
Leonore M
LM
D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004032:Diet; D015536:Down-Regulation; D004734:Energy Metabolism / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014280:Triglycerides / Q000008:administration & dosage / Q000378:metabolism*
D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014280:Triglycerides; D000431:Ethanol; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins