Memon R A, Feingold K R, Moser A H, Fuller J, Grunfeld C
Department of Medicine, University of California, San Francisco 94143, USA.
Am J Physiol. 1998 Feb;274(2):E210-7. doi: 10.1152/ajpendo.1998.274.2.E210.
The cloning of two novel fatty acid (FA) transport proteins, FA transport protein (FATP) and FA translocase (FAT), has recently been reported; however, little is known about their in vivo regulation. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) stimulate adipose tissue lipolysis and enhance hepatic lipogenesis and reesterification while suppressing FA oxidation in multiple tissues. Hence, in this study we examined their effects on FATP and FAT mRNA levels in Syrian hamsters. Our results demonstrate that LPS decreased FATP and FAT mRNA expression in adipose tissue, heart, skeletal muscle, brain, spleen, and kidney, tissues in which FA uptake and/or oxidation is decreased during sepsis. In the liver, where FA oxidation is decreased during sepsis but the uptake of peripherally derived FA is increased to support reesterification, LPS decreased FATP mRNA expression by 70-80% but increased FAT mRNA levels by four- to fivefold. The effects of LPS on FATP and FAT mRNA levels in liver were observed as early as 4 h after administration and were maximal by 16 h. TNF and IL-1 mimicked the effect of LPS on FATP and FAT mRNA levels in both liver and adipose tissue. These results indicate that the mRNAs for both transport proteins are downregulated by LPS in tissues in which FA uptake and/or oxidation are decreased during sepsis. On the other hand, differential regulation of FATP and FAT mRNA in liver raises the possibility that these proteins may be involved in transporting FA to different locations inside the cell. FATP may transport FA toward mitochondria for oxidation, which is decreased in sepsis, whereas FAT may transport FA to cytosol for reesterification, which is enhanced in sepsis.
最近有报道称克隆出了两种新型脂肪酸（FA）转运蛋白，即脂肪酸转运蛋白（FATP）和脂肪酸转位酶（FAT）；然而，对于它们在体内的调节机制却知之甚少。内毒素[脂多糖（LPS）]、肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）可刺激脂肪组织脂解，增强肝脏脂肪生成和再酯化作用，同时抑制多种组织中的脂肪酸氧化。因此，在本研究中，我们检测了它们对叙利亚仓鼠体内FATP和FAT mRNA水平的影响。我们的结果表明，LPS降低了脂肪组织、心脏、骨骼肌、脑、脾脏和肾脏中FATP和FAT mRNA的表达，在脓毒症期间这些组织中的脂肪酸摄取和/或氧化减少。在肝脏中，脓毒症期间脂肪酸氧化减少，但外周来源脂肪酸的摄取增加以支持再酯化，LPS使FATP mRNA表达降低70 - 80%，但使FAT mRNA水平增加4至5倍。LPS给药后4小时即可观察到其对肝脏中FATP和FAT mRNA水平的影响，16小时时达到最大。TNF和IL-1在肝脏和脂肪组织中模拟了LPS对FATP和FAT mRNA水平的影响。这些结果表明，在脓毒症期间脂肪酸摄取和/或氧化减少的组织中，LPS可下调这两种转运蛋白的mRNA水平。另一方面，肝脏中FATP和FAT mRNA的差异调节增加了这些蛋白可能参与将脂肪酸转运至细胞内不同位置的可能性。FATP可能将脂肪酸转运至线粒体进行氧化，脓毒症时氧化减少，而FAT可能将脂肪酸转运至胞质溶胶进行再酯化，脓毒症时再酯化增强。
