Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
J Cell Biochem. 2010 Oct 1;111(2):497-507. doi: 10.1002/jcb.22734.
Palmitate negatively affects insulin secretion and apoptosis in the pancreatic β-cell. The detrimental effects are abolished by elongating and desaturating the fatty acid into oleate. To investigate mechanisms of how the two fatty acids differently affect β-cell function and apoptosis, lipid handling was determined in MIN6 cells cultured in the presence of the fatty acids palmitate (16:0) and oleate (18:1) and also corresponding monounsaturated fatty acid palmitoleate (16:1) and saturated fatty acid stearate (18:0). Insulin secretion was impaired and apoptosis accentuated in palmitate-, and to some extent, stearate-treated cells. Small or no changes in secretion or apoptosis were observed in cells exposed to palmitoleate or oleate. Expressions of genes associated with fatty acid esterification (SCD1, DGAT1, DGAT2, and FAS) were augmented in cells exposed to palmitate or stearate but only partially (DGAT2) in palmitoleate- or oleate-treated cells. Nevertheless, levels of triglycerides were highest in cells exposed to oleate. Similarly, fatty acid oxidation was most pronounced in oleate-treated cells despite comparable up-regulation of CPT1 after treatment of cells with the four different fatty acids. The difference in apoptosis between palmitate and stearate was paralleled by similar differences in levels of markers of endoplasmic reticulum (ER) stress in cells exposed to the two fatty acids. Palmitate-induced ER stress was not accounted for by ceramide de novo synthesis. In conclusion, although palmitate initiated stronger expression changes consistent with lipid accumulation and combustion in MIN6 cells, rise in triglyceride levels and fatty acid oxidation was favored specifically in cells exposed to oleate.
棕榈酸会对胰岛β细胞的胰岛素分泌和细胞凋亡产生负面影响。而将脂肪酸延伸并使其不饱和可以消除这种有害影响，将其转化为油酸。为了研究这两种脂肪酸如何以不同的方式影响β细胞功能和细胞凋亡，我们在 MIN6 细胞中培养，并在培养基中加入棕榈酸（16:0）和油酸（18:1），以及对应的单不饱和脂肪酸棕榈油酸（16:1）和饱和脂肪酸硬脂酸（18:0），以确定细胞内脂质代谢情况。棕榈酸（16:0）和硬脂酸（18:0）处理的细胞中，胰岛素分泌受损，细胞凋亡加剧，而棕榈油酸（16:1）和油酸（18:1）处理的细胞中，胰岛素分泌或细胞凋亡几乎没有变化。暴露于棕榈酸或硬脂酸的细胞中与脂肪酸酯化相关的基因（SCD1、DGAT1、DGAT2 和 FAS）表达增加，但在棕榈油酸或油酸处理的细胞中，仅部分基因（DGAT2）表达增加。然而，暴露于油酸的细胞中甘油三酯水平最高。同样，尽管在四种不同的脂肪酸处理细胞后，CPT1 的表达均上调，但油酸处理的细胞中脂肪酸氧化最为明显。尽管棕榈酸和硬脂酸诱导的细胞凋亡存在差异，但暴露于这两种脂肪酸的细胞中内质网（ER）应激标志物的水平也存在类似差异。棕榈酸诱导的 ER 应激不能用神经酰胺从头合成来解释。总之，尽管棕榈酸在 MIN6 细胞中引发了更强的表达变化，这些变化与脂质积累和燃烧一致，但只有在暴露于油酸的细胞中，甘油三酯水平的升高和脂肪酸氧化才会得到促进。
