A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders.
Proc Natl Acad Sci U S A
; 96(13): 7473-8, 1999 Jun 22.
Article
em En
| MEDLINE
| ID: mdl-10377439
ABSTRACT
We hypothesized that the lipid-activated transcription factor, the peroxisome proliferator-activated receptor alpha (PPARalpha), 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 PPARalpha (PPARalpha-/-), a phenotype that bears remarkable similarity to that of humans with genetic defects in mitochondrial fatty acid oxidation enzymes. In PPARalpha+/+ mice, fasting induced the hepatic and cardiac expression of PPARalpha 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 PPARalpha target genes was not induced by fasting in PPARalpha-/- mice. These results define a critical role for PPARalpha in a transcriptional regulatory response to fasting and identify the PPARalpha-/- mouse as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Jejum
/
Receptores Citoplasmáticos e Nucleares
/
Ácidos Graxos
/
Fígado
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos