Fatty acid-induced oxidation and triglyceride formation is higher in insulin-producing MIN6 cells exposed to oleate compared to palmitate.

ABSTRACT

Palmitate negatively affects insulin secretion and apoptosis in the pancreatic ß-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 ß-cell function and apoptosis, lipid handling was determined in MIN6 cells cultured in the presence of the fatty acids palmitate (160) and oleate (181) and also corresponding monounsaturated fatty acid palmitoleate (161) and saturated fatty acid stearate (180). 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.