标题：A critical role for the peroxisome proliferator-activated receptor α (PPARα) in the cellular fasting response: The PPARα-null mouse as a model of fatty acid oxidation disorders
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：13
页码：7473-7478
DOI：10.1073/pnas.96.13.7473
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We hypothesized that the lipid-activated transcription factor, the peroxisome proliferator-activated receptor (PPAR), plays a pivotal role in the cellular metabolic response to fasting. Short-term starvation caused hepatic steatosis, myocardial lipid accumulation, and hypoglycemia, with an inadequate ketogenic response in adult mice lacking PPAR (PPAR-/-), a phenotype that bears remarkable similarity to that of humans with genetic defects in mitochondrial fatty acid oxidation enzymes. In PPAR+/+ mice, fasting induced the hepatic and cardiac expression of PPAR target genes encoding key mitochondrial (medium-chain acyl-CoA dehydrogenase, carnitine palmitoyltransferase I) and extramitochondrial (acyl-CoA oxidase, cytochrome P450 4A3) enzymes. In striking contrast, the hepatic and cardiac expression of most PPAR target genes was not induced by fasting in PPAR-/- mice. These results define a critical role for PPAR in a transcriptional regulatory response to fasting and identify the PPAR-/- mouse as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization.
