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

Citation
Kajm. Van Der Lee et al., Fasting-induced changes in the expression of genes controlling substrate metabolism in the rat heart, J LIPID RES, 42(11), 2001, pp. 1752-1758
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF LIPID RESEARCH
ISSN journal
0022-2275 → ACNP
Volume
42
Issue
11
Year of publication
2001
Pages
1752 - 1758
Database
ISI
SICI code
0022-2275(200111)42:11<1752:FCITEO>2.0.ZU;2-L
Abstract
During fasting, when overall metabolism changes, the contribution of glucos e and fatty acids (FA) to cardiac energy production alters as well. Here, w e 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 express ion of genes coding for glucose-handling proteins (glucose transporter GLUT 4, 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 met abolism (FA translocase/CD36, muscle-type carnitine palmitoyl transferase 1 , long-chain acyl-CoA dehydrogenase) and of the uncoupling protein UCP-3 in creased over 50% in hearts of fasted rats. Surprisingly, mRNA levels of the fatty acid-activated transcription factors PPAR alpha and PPAR beta/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 admini stration during the final 8 h of fasting did not affect the expression of t he majority of metabolic genes, but totally abolished the induction of UCP- 3. In conclusion, the adult rat heart responds to changes in nutritional st atus, as provoked by 46 h fasting, through adjustment of glucose as well as FA metabolism at the level of gene expression.