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
摘要：
We hypothesized that the lipid-activated transcription factor, the peroxisome proliferator-activated receptor α (PPARα), 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 PPARα (PPARα -/-), a phenotype that bears remarkable similarity to that of humans with genetic defects in mitochondrial fatty acid oxidation enzymes. In PPARα +/+ mice, fasting induced the hepatic and cardiac expression of PPARα 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 PPARα target genes was not induced by fasting in PPARα -/- mice. These results define a critical role for PPARα in a transcriptional regulatory response to fasting and identify the PPARα -/- mouse as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization.
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DOI：
10.1073/pnas.96.13.7473
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年份：
1999
万方医学
掌桥科研
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