Luiken J J F P, Koonen D P Y, Coumans W A, Pelsers M M A L, Binas B, Bonen A, Glatz J F C
Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, NL-6200 MD Maastricht, The Netherlands.
Lipids. 2003 Apr;38(4):491-6. doi: 10.1007/s11745-003-1089-6.
Previous studies with cardiac myocytes from homozygous heart-type fatty acid (FA)-binding protein (H-FABP) -/- mice have indicated that this intracellular receptor protein for long-chain FA is involved in the cellular uptake of these substrates. Based on the knowledge that muscle FA uptake is a process highly sensitive to regulation by hormonal and mechanical stimuli, we studied whether H-FABP would play a role in this regulation. A suitable model system to answer this question is provided by H-FABP +/- mice, because in hindlimb muscles the content of H-FABP was measured to be 34% compared to wild-type mice. In these H-FABP +/- skeletal muscles, just as in H-FABP -/- muscles, contents of FA transporters, i.e., 43-kDa FABPpm and 88-kDa FAT/CD36, were similar compared to wild-type muscles, excluding possible compensatory mechanisms at the sarcolemmal level. Palmitate uptake rates were measured in giant vesicles prepared from hindlimb muscles of H-FABP -/-, H-FABP +/-, and H-FABP +/+ mice. For comparison, giant vesicles were isolated from liver, the tissue of which expresses a distinct type of FABP (i.e., L-FABP). Whereas in H-FABP -/- skeletal muscle FA uptake was reduced by 42-45%, FA uptake by H-FABP +/- skeletal muscle was not different from that in wild-type mice. In contrast, in liver from H-FABP -/- and from H-FABP +/- mice, FA uptake was not altered compared to wild-type animals, indicating that changes in FA uptake are restricted to H-FABP expressing tissues. It is concluded that H-FABP plays an important, yet merely permissive, role in FA uptake into muscle tissues.
先前对纯合子心脏型脂肪酸（FA）结合蛋白（H-FABP）基因敲除小鼠心肌细胞的研究表明，这种长链FA的细胞内受体蛋白参与了这些底物的细胞摄取过程。基于肌肉FA摄取是一个对激素和机械刺激调节高度敏感的过程这一认识，我们研究了H-FABP是否会在这种调节中发挥作用。H-FABP基因杂合小鼠为回答这个问题提供了一个合适的模型系统，因为在后肢肌肉中，与野生型小鼠相比，H-FABP的含量经测定为34%。在这些H-FABP基因杂合的骨骼肌中，与H-FABP基因敲除的肌肉一样，FA转运蛋白（即43-kDa FABPpm和88-kDa FAT/CD36）的含量与野生型肌肉相比相似，排除了肌膜水平可能的代偿机制。在从H-FABP基因敲除、H-FABP基因杂合和H-FABP基因野生型小鼠后肢肌肉制备的巨大囊泡中测量了棕榈酸摄取率。作为比较，从肝脏分离出巨大囊泡，肝脏组织表达一种不同类型的FABP（即L-FABP）。虽然在H-FABP基因敲除的骨骼肌中FA摄取减少了42%-45%，但H-FABP基因杂合的骨骼肌中的FA摄取与野生型小鼠没有差异。相反，在H-FABP基因敲除和H-FABP基因杂合小鼠的肝脏中，与野生型动物相比，FA摄取没有改变，这表明FA摄取的变化仅限于表达H-FABP的组织。结论是，H-FABP在FA摄取到肌肉组织中起着重要但仅仅是允许性的作用。
