Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes
Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes
复制标题
DOI：
10.1111/apha.12022
复制
发表时间：
2013-02-01
影响因子：
6.3
通讯作者：
Gorski, J.
中科院分区：
文献类型：
--
作者：
Chabowski, A.;Zendzian-Piotrowska, M.;Gorski, J.
目的确定FAT/CD36、FABPpm和FATP-2转运体在原代肝细胞中(i)脂肪酸跨质膜运动和（ii）棕榈酸（PA）和油酸（OA）脂肪酸诱导胰岛素抵抗中的存在和可能参与。方法分别用PA和OA或联合使用FA转运激活剂（AICAR、胰岛素）或抑制剂（SSO、根皮素）治疗原代肝细胞。使用Western blot分析测定FA和葡萄糖转运蛋白以及胰岛素信号蛋白的表达。用放射性同位素测量棕榈酸盐和葡萄糖的转运。细胞内脂质含量[神经酰胺、二酰基甘油（DG）和三酰基甘油]和FA组成通过GLC测定。结果在原代肝细胞中，加入根皮素可降低胰岛素，AICAR可促进棕榈酸盐转运。PA和OA脂肪酸均诱导了FAT/CD36和FATP-2的蛋白表达，同时伴有：(i) GLUT-2蛋白含量的降低，（ii）胰岛素刺激的葡萄糖摄取的抑制，（iii）胰岛素刺激的AKT和GSK激活的减少，（iv） DG （PA和OA）或神经酰胺（仅PA）的积累。结论FA转运至肝细胞至少部分是蛋白介导的过程，PA和OA均可诱导FAT/CD36和FATP-2的蛋白表达。饱和脂肪酸（PA）和不饱和脂肪酸（OA）都会诱导原代肝细胞的胰岛素抵抗，这与DG和/或神经酰胺的积累有关。
Aims To determine the presence and possible involvement of FAT/CD36, FABPpm and FATP-2, transporters in (i) fatty acids movement across plasma membrane and (ii) an induction of insulin resistance by palmitic (PA) and oleic (OA) fatty acids in primary hepatocytes. Methods Primary hepatocytes were treated with either PA and OA or combination of activators (AICAR, Insulin) or inhibitors (SSO, phloretin) of FA transport. Expression of FA and glucose transporters as well as insulin signalling proteins was determined using Western blot analyses. Palmitate and glucose transport was measured using radioactive isotopes. Intracellular lipid content [ceramide, diacylglycerols (DG) and triacylglycerols] and FA composition were estimated by GLC. Results In primary hepatocytes, adding phloretin diminished insulin, and AICAR stimulated palmitate transport. Both PA and OA fatty acids induced the protein expression of FAT/CD36 and FATP-2 with concomitant: (i) reduction in GLUT-2 protein content, (ii) inhibition of insulin-stimulated glucose uptake, (iii) reduction in insulin-stimulated activation of AKT and GSK, (iv) accumulation of either DG (PA and OA) or ceramide (only PA). Conclusions FA transport into hepatocytes is, at least in part, protein-mediated process, and both PA and OA induce the protein expression of FAT/CD36 and FATP-2. Both saturated (PA) and unsaturated (OA) fatty acids induce insulin resistance in primary hepatocytes, associated with the accumulation of DG and/or ceramide.