Fasting-induced changes in the expression of genes controlling substrate metabolism in the rat heart.
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 PPARalpha and PPARbeta/delta were reduced in hearts of fasted rats, whereas in livers, fasting led to a marked rise in PPARalpha 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
KA
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
Willemsen
P H
PH
Samec
S
S
Seydoux
J
J
Dulloo
A G
AG
Pelsers
M M
MM
Glatz
J F
JF
Van der Vusse
G J
GJ
Van Bilsen
M
M
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D018955:CD36 Antigens; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000502:physiology*; D005227:Fatty Acids / Q000097:blood; D015870:Gene Expression; D051275:Glucose Transporter Type 4; D006593:Hexokinase / Q000235:genetics; D007473:Ion Channels; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology; D027361:Organic Anion Transporters / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000071247:Uncoupling Protein 3
D001786:Blood Glucose; D018955:CD36 Antigens; D002352:Carrier Proteins; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D007473:Ion Channels; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D009525:Niacin; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002334:Carnitine O-Palmitoyltransferase; D006593:Hexokinase