[HTML][HTML] Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting

S Kersten, J Seydoux, JM Peters… - The Journal of …, 1999 - Am Soc Clin Investig
The Journal of clinical investigation, 1999Am Soc Clin Investig
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 α (PPARα) was found to play a role in regulating mitochondrial and peroxisomal
fatty acid oxidation, suggesting that PPARα may be involved in the transcriptional response
to fasting. To investigate this possibility, PPARα-null mice were subjected to a high fat diet or …
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 α (PPARα) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARα may be involved in the transcriptional response to fasting. To investigate this possibility, PPARα-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARα-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARα-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, PPARα mRNA is induced during fasting in wild-type mice. The data indicate that PPARα plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARα stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.
The Journal of Clinical Investigation