Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes
Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes
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DOI：
10.1111/j.1440-1746.2008.05733.x
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发表时间：
2009-05-01
影响因子：
4.1
通讯作者：
Loria, Paola
中科院分区：
文献类型：
--
作者：
Ricchi, Matteo;Odoardi, Maria Rosaria;Loria, Paola
研究表明，单不饱和油酸的毒性低于棕榈酸，并且可以在体外脂肪变性模型中预防/减轻棕榈酸肝细胞毒性。然而，这些影响在多大程度上是由脂肪变性程度介导的尚不清楚。我们评估了脂肪变性本身是否与肝细胞凋亡相关，并确定了油酸和棕榈酸（西方饮食中最丰富的脂肪酸）在三种肝细胞系（HepG2、HuH7、WRL68）诱导的脂肪变性体外模型中对甘油三酯积累和细胞凋亡的作用。评估单独或组合（摩尔比 2:1）油酸（0.66 和 1.32 mM）和棕榈酸（0.33 和 0.66 mM）孵育 24 小时对脂肪变性、细胞凋亡和胰岛素信号传导的影响。与 PPAR γ 和 SREBP-1 基因激活同时，用油酸处理细胞时的脂肪变性程度比用棕榈酸处理时更大；后一种脂肪酸与 PPAR α 表达增加有关。细胞凋亡与脂肪变性沉积成反比。此外，棕榈酸而非油酸会损害胰岛素信号传导。尽管两种脂肪酸组合孵育产生的脂肪量较高，但细胞凋亡率和受损的胰岛素信号传导低于单独用棕榈酸处理的细胞，这表明油酸具有保护作用。在肝细胞培养物中，油酸比棕榈酸更具脂肪生成性，但细胞凋亡较少。这些数据可能为非酒精性脂肪肝的饮食模式和发病模型的临床发现提供生物学基础。
Studies have shown monounsaturated oleic acid to be less toxic than palmitic acid and to prevent/attenuate palmitic acid hepatocites toxicity in steatosis models in vitro. However, to what degree these effects are mediated by steatosis extent is unknown.We evaluated whether steatosis per se is associated with hepatocytes apoptosis and determined the role of oleic and palmitic acid, the most abundant fatty acids in western diets, on triglyceride accumulation and apoptosis in an in vitro model of steatosis induced in three hepatocytic cell lines (HepG2, HuH7, WRL68). The impact of incubation for 24 h with oleic (0.66 and 1.32 mM) and palmitic acid (0.33 and 0.66 mM), alone or combined (molar ratio 2 : 1) on steatosis, apoptosis, and insulin signalling, was evaluated.Concurrent with PPAR gamma and SREBP-1 gene activation, steatosis extent was larger when cells were treated with oleic than with palmitic acid; the latter fatty acid was associated with increased PPAR alpha expression. Cell apoptosis was inversely proportional to steatosis deposition. Moreover, palmitic, but not oleic acid, impaired insulin signalling. Despite the higher amount of fat resulting from incubation of the two fatty acids combined, the apoptosis rate and impaired insulin signalling were lower than in cells treated with palmitic acid alone, indicating a protective effect of oleic acid.Oleic acid is more steatogenic but less apoptotic than palmitic acid in hepatocityc cell cultures. These data may provide a biological basis for clinical findings on dietary patterns and pathogenetic models of nonalcoholic fatty liver disease.