Fatty acid-induced toxicity and neutral lipid accumulation in insulin-producing RINm5F cells
Fatty acid-induced toxicity and neutral lipid accumulation in insulin-producing RINm5F cells
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DOI：
10.1016/j.tiv.2006.02.007
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发表时间：
2006-10-01
影响因子：
3.2
通讯作者：
Curi, Rui
中科院分区：
文献类型：
--
作者：
Azevedo-Martins, Anna Karenina;Monteiro, Ariana Pereira;Curi, Rui
已有研究表明，脂肪酸可导致大鼠和人类原代胰岛β细胞以及胰岛素产生细胞系的死亡。这些研究主要集中在饱和和单不饱和脂肪酸，如棕榈酸、硬脂酸和油酸。在这项研究中，我们对更广泛的FA的毒性进行了比较。用流式细胞仪检测细胞质膜完整性丧失和DNA片段化增加来评价不同FA对胰岛素产生的RINm5F细胞的毒性作用。此外，还测定了FA诱导的中性脂肪堆积和FA的组成。棕榈酸、亚油酸、伽马亚麻酸、油酸、硬脂酸和二十碳五烯酸导致产生胰岛素的RINm5F细胞的DNA断裂。膜完整性损失主要是由亚油酸和7-亚麻酸引起的。经高效液相分析，细胞毒性与细胞内FA的丰度无关。总体而言，FA对产生胰岛素的RINm5F细胞的毒性作用与其链长和不饱和程度无关。在这些细胞中，PA和LA表现出最高的毒性，而AA没有毒性。此外，除AA和EPA外，大多数受试FA的毒性与低NLA呈负相关。这项研究的结果有助于理解FA在2型糖尿病和肥胖症中发生的胰岛β细胞功能损害中的作用。(C)2006爱思唯尔有限公司。保留所有权利。
Fatty acids have been shown to cause death of rat and human primary pancreatic beta cells and of insulin-producing cell lines. These studies focused mainly on saturated and monounsaturated FA such as palmitic, stearic and oleic acids. In this study, we have performed a comparison of the toxicity of a wider range of FA. The toxicity of different FA to insulin-producing RINm5F cells was assessed by flow cytometry measuring loss of plasma membrane integrity and increase in DNA fragmentation. Additionally, the FA induced neutral lipid accumulation and the FA composition were determined. Palmitic, linoleic, gamma-linolenic, oleic, stearic, and eicosapentaenoic acid caused DNA fragmentation of insulin-producing RINm5F cells. Loss of membrane integrity was mainly caused by linoleic and 7-linolenic acid. There was no correlation between cytotoxicity and the abundance of the FA in the cells as determined by HPLC analysis. Taken as whole, the toxic effect of the FA on insulin-producing RINm5F cells varied irrespective of the chain length and the degree of unsaturation. In these cells PA and LA exhibited the highest toxicity, whereas AA was not toxic. In addition, the toxicity of most tested FA was inversely related to low NLA, except for AA and EPA. The results of this study contribute to the understanding of the role of FA in the impairment of pancreatic beta cell function that occurs in type 2 diabetes and obesity. (c) 2006 Elsevier Ltd. All rights reserved.