Van der Lee K A, Willemsen P H, Samec S, Seydoux J, Dulloo A G, Pelsers M M, Glatz J F, Van der Vusse G J, Van Bilsen M
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
J Lipid Res. 2001 Nov;42(11):1752-8.
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.
在禁食期间，当整体新陈代谢发生变化时，葡萄糖和脂肪酸（FA）对心脏能量产生的贡献也会改变。在此，我们研究了心脏是否能够通过调节其基因表达来适应这种禁食诱导的变化。将大鼠随意喂食或禁食46小时，导致循环葡萄糖水平降低，脂肪酸水平升高3倍。除了参与葡萄糖或脂肪酸代谢的蛋白质的心脏活性或含量发生变化外，mRNA水平也发生了改变。与喂食的大鼠相比，禁食大鼠中编码葡萄糖处理蛋白（葡萄糖转运蛋白GLUT4、己糖激酶I和II）的基因的心脏表达降低了70%。相反，禁食大鼠心脏中参与脂肪酸转运和代谢的各种基因（脂肪酸转位酶/CD36、肌肉型肉碱棕榈酰转移酶1、长链酰基辅酶A脱氢酶）以及解偶联蛋白UCP-3的mRNA水平增加了50%以上。令人惊讶的是，禁食大鼠心脏中脂肪酸激活的转录因子PPARα和PPARβ/δ的mRNA水平降低，而在肝脏中，禁食导致PPARα mRNA显著升高。在禁食的最后8小时内通过给予烟酸降低脂肪酸水平并不影响大多数代谢基因的表达，但完全消除了UCP-3的诱导。总之，成年大鼠心脏通过在基因表达水平上调整葡萄糖以及脂肪酸代谢来响应46小时禁食所引发的营养状况变化。
