Peroxisome proliferator-activated receptor [small alpha, Greek] mediates the adaptive response to fasting.
Kersten, Sander; Seydoux, Josiane; Peters, Jeffrey M.; Gonzalez, Frank J.; Desvergne, Beatrice; Wahli, Walter
[Miscellaneous Article] Journal of Clinical Investigation. 103(11):1489-1498, June 1999.

(Format: HTML)

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 [small alpha, Greek] (PPAR[small alpha, Greek]) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPAR[small alpha, Greek] may be involved in the transcriptional response to fasting. To investigate this possibility, PPAR[small alpha, Greek]-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wildtype mice. PPAR[small alpha, Greek]-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPAR[small alpha, Greek]-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, PPAR[small alpha, Greek] mRNA is induced during fasting in wildtype mice. The data indicate that PPAR[small alpha, Greek] plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPAR[small alpha, Greek] stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.

J.Clin. Invest. 103:1489-1498 (1999).

Copyright (C) 1999 The American Society for Clinical Investigation, Inc.