Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.
Data(s) |
01/06/1999
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Resumo |
Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPARalpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARalpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPARalpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARalpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARalpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPARalpha mRNA is induced during fasting in wild-type mice. The data indicate that PPARalpha plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_777493C2C963 isbn:0021-9738[print], 0021-9738[linking] pmid:10359558 doi:10.1172/JCI6223 isiid:000083468100004 |
Idioma(s) |
en |
Fonte |
Journal of Clinical Investigation, vol. 103, no. 11, pp. 1489-1498 |
Palavras-Chave | #Acyl-CoA Dehydrogenase; Adaptation, Physiological/physiology; Animals; Apolipoproteins B/genetics; Apolipoproteins E/genetics; Carnitine O-Palmitoyltransferase/genetics; Carrier Proteins/genetics; Dietary Fats/metabolism; Fasting; Fatty Acid Desaturases/genetics; Fatty Acid-Binding Proteins; Fatty Acids/metabolism; Fatty Liver/metabolism; Gene Expression; Gene Expression Regulation; Hormones/metabolism; Hypothermia, Induced; Lipoproteins, VLDL/secretion; Mice; Mice, Knockout; Microbodies; Myelin P2 Protein/genetics; Neoplasm Proteins; Nerve Tissue Proteins; Oxidation-Reduction; Phenotype; RNA, Messenger; Receptors, Cytoplasmic and Nuclear/genetics; Receptors, Cytoplasmic and Nuclear/metabolism; Signal Transduction; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic |
Tipo |
info:eu-repo/semantics/article article |