120
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.

      The Journal of clinical investigation

      Acyl-CoA Dehydrogenase, Adaptation, Physiological, physiology, Animals, Apolipoproteins B, genetics, Apolipoproteins E, Carnitine O-Palmitoyltransferase, Carrier Proteins, Dietary Fats, metabolism, Fasting, Fatty Acid Desaturases, Fatty Acid-Binding Proteins, Fatty Acids, Fatty Liver, Gene Expression, Gene Expression Regulation, Hormones, Hypothermia, Induced, Lipoproteins, VLDL, secretion, Mice, Mice, Knockout, Microbodies, Myelin P2 Protein, Neoplasm Proteins, Nerve Tissue Proteins, Oxidation-Reduction, Phenotype, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Signal Transduction, Transcription Factors, Transcription, Genetic

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Author and article information

          Journal
          10359558
          408372
          10.1172/JCI6223

          Comments

          Comment on this article