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J. Lipid Res.
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Journal of Lipid Research, Vol. 42, 1752-1758, November 2001
Copyright © 2001 by Lipid Research, Inc.

Fasting-induced changes in the expression of genes controlling substrate metabolism in the rat heart

Karin A. J. M. Van der Leea, Peter H. M. Willemsena, Sonia Samecb, Josiane Seydouxc, Abdul G. Dulloob, Maurice M. A. L. Pelsersa, Jan F. C. Glatza, Ger J. Van der Vussea, and Marc Van Bilsena
a Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
b Institute of Physiology, University of Fribourg, Fribourg, Switzerland
c Department of Physiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

Correspondence to: Marc Van Bilsen, To whom correspondence should be addressed., Marc.vanBilsen{at}FYS.Unimaas.NL (E-mail)

During fasting, when overall metabolism changes, the contribution of glucose and fatty acids (FA) to cardiac energy production alters as well. Here, we examined if the heart is able to adapt to such fasting-induced changes by modulation of its gene expression. Rats were fed ad libitum or fasted for 46 h, resulting in reduced circulating glucose levels and a 3-fold rise in FA. Besides changes in the cardiac activity or content of proteins involved in glucose or FA metabolism, mRNA levels also altered. The cardiac expression of genes coding for glucose-handling proteins (glucose transporter GLUT4, hexokinase I and II) was up to 70% lower in fasted than in fed rats. In contrast, the mRNA levels of various genes involved in FA transport and metabolism (FA translocase/CD36, muscle-type carnitine palmitoyl transferase 1, long-chain acyl-CoA dehydrogenase) and of the uncoupling protein UCP-3 increased over 50% in hearts of fasted rats. Surprisingly, mRNA levels of the fatty acid- activated transcription factors PPAR{alpha} and PPARß/{delta} were reduced in hearts of fasted rats, whereas in livers, fasting led to a marked rise in PPAR{alpha} mRNA. Reducing FA levels by nicotinic acid administration during the final 8 h of fasting did not affect the expression of the majority of metabolic genes, but totally abolished the induction of UCP-3.

In conclusion, the adult rat heart responds to changes in nutritional status, as provoked by 46 h fasting, through adjustment of glucose as well as FA metabolism at the level of gene expression. —Van der Lee, K. A. J. M., P. H. M. Willemsen, S. Samec, J. Seydoux, A. G. Dulloo, M. M. A. L. Pelsers, J. F. C. Glatz, G. J. Van der Vusse, and M. Van Bilsen. Fasting-induced changes in the expression of genes controlling substrate metabolism in the rat heart. J. Lipid Res. 2001. 42: 1752–1758.

Supplementary key words: fatty acids, gene expression, nicotinic acid, uncoupling proteins, peroxisome proliferator-activated receptor


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