Chabowski Adrian, Górski Jan, Glatz Jan F C, P Luiken Joost J F, Bonen Arend
Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland.
Curr Cardiol Rev. 2008 Feb;4(1):12-21. doi: 10.2174/157340308783565429.
Long chain fatty acids (LCFAs) provide 70-80% of the energy for cardiac contractile activity. LCFAs are also essential for many other cellular functions, such as transcriptional regulation of proteins involved in lipid metabolism, modulation of intracellular signalling pathways, and as substrates for membrane constituents. When LCFA uptake exceeds the capacity for their cardiac utilization, the intracellular lipids accumulate and are thought to contribute to contractile dysfunction, arrhythmias, cardiac myocyte apoptosis and congestive heart failure. Moreover, increased cardiac myocyte triacylglycerol, diacylglycerol and ceramide depots are cardinal features associated with obesity and type 2 diabetes. In recent years considerable evidence has accumulated to suggest that, the rate of entry of long chain fatty acids (LCFAs) into the cardiac myocyte is a key factor contributing to a) regulating cardiac LCFA metabolism and b) lipotoxicity in the obese and diabetic heart. In the present review we i) examine the evidence indicating that LCFA transport into the heart involves a protein-mediated mechanism, ii) discuss the proteins involved in this process, including FAT/CD36, FABPpm and FATP1, iii) discuss the mechanisms involved in regulating LCFA transport by some of these proteins (including signaling pathways), as well as iv) the possible interactions of these proteins in regulating LCFA transport into the heart. In addition, v) we discuss how LCFA transport and transporters are altered in the obese/diabetic heart.
长链脂肪酸（LCFAs）为心脏收缩活动提供70 - 80%的能量。LCFAs对许多其他细胞功能也至关重要，例如参与脂质代谢的蛋白质的转录调控、细胞内信号通路的调节以及作为膜成分的底物。当LCFA摄取量超过心脏对其的利用能力时，细胞内脂质会积累，并被认为会导致收缩功能障碍、心律失常、心肌细胞凋亡和充血性心力衰竭。此外，心肌细胞中三酰甘油、二酰甘油和神经酰胺储存量增加是肥胖和2型糖尿病相关的主要特征。近年来，大量证据表明，长链脂肪酸（LCFAs）进入心肌细胞的速率是导致以下两方面的关键因素：a）调节心脏LCFA代谢；b）肥胖和糖尿病心脏中的脂毒性。在本综述中，我们：i）研究表明LCFA转运至心脏涉及蛋白质介导机制的证据；ii）讨论参与此过程的蛋白质，包括FAT/CD36、FABPpm和FATP1；iii）讨论其中一些蛋白质（包括信号通路）调节LCFA转运所涉及的机制；iv）这些蛋白质在调节LCFA转运至心脏过程中可能的相互作用。此外，v）我们讨论肥胖/糖尿病心脏中LCFA转运和转运蛋白是如何改变的。
