Protective effects of arachidonic acid against palmitic acid-mediated lipotoxicity in HIT-T15 cells
Protective effects of arachidonic acid against palmitic acid-mediated lipotoxicity in HIT-T15 cells
复制标题
DOI：
10.1007/s11010-011-1200-z
复制
发表时间：
2012-05-01
影响因子：
4.3
通讯作者：
Cheon, Hyae Gyeong
中科院分区：
文献类型：
--
作者：
Cho, Young Sik;Kim, Chi Hyun;Cheon, Hyae Gyeong
饱和脂肪酸被认为是2型糖尿病的主要促成因素，而不饱和脂肪酸对预防糖尿病的发展具有有益作用。然而，多不饱和脂肪酸在胰腺β细胞中的作用尚未报道。在这里，我们研究了花生四烯酸（AA）对棕榈酸（PA）介导的脂毒性克隆HIT-T15胰腺β细胞的影响。AA阻止PA诱导的脂毒性所示的细胞活力，DNA片段化和线粒体膜电位，而二十碳四炔酸（ETYA），非代谢的AA，对PA诱导的脂毒性的影响不大。与其对PA诱导的脂毒性的保护作用平行，AA恢复PA诱导的受损胰岛素表达和分泌。与单独的PA相比，AA而不是ETYA增加了PA存在下的细胞内甘油三酯（TG），黄腐酚，二酰基甘油酰基转移酶（DGAT）抑制剂，逆转了AA诱导的PA保护作用。两者合计，我们的研究结果表明，AA保护PA诱导的脂毒性克隆HIT-T15胰腺β细胞，和保护作用可能与TG积累，可能通过隔离脂毒性PA进入TG。
Saturated fatty acids have been considered major contributing factors in type 2 diabetes, whereas unsaturated fatty acids have beneficial effects for preventing the development of diabetes. However, the effects of polyunsaturated fatty acids in pancreatic beta cells have not been reported. Here, we examined the effects of arachidonic acid (AA) on palmitic acid (PA)-mediated lipotoxicity in clonal HIT-T15 pancreatic beta cells. AA prevented the PA-induced lipotoxicity as indicated by cell viability, DNA fragmentation and mitochondrial membrane potential, whereas eicosatetraynoic acid (ETYA), a non-metabolizable AA, had little effect on PA-induced lipotoxicity. In parallel with its protective effects against PA-induced lipotoxicity, AA restored impaired insulin expression and secretion induced by PA. AA but not ETYA increased intracellular triglyceride (TG) in the presence of PA compared with PA alone, and xanthohumol, a diacylglycerol acyltransferase (DGAT) inhibitor, reversed AA-induced protection from PA. Taken together, our results suggest that AA protects against PA-induced lipotoxicity in clonal HIT-T15 pancreatic beta cells, and the protective effects may be associated with TG accumulation, possibly through sequestration of lipotoxic PA into TG.