János Bolyai Research Scholarship of the Hungarian Academy of Sciences
(K125201) Támogató: NKFIH
High fatty acid (FA) levels are deleterious to pancreatic β-cells, largely due to
the accumulation of biosynthetic lipid intermediates, such as ceramides and diglycerides,
which induce ER stress and apoptosis. Toxicity of palmitate (16:0) and oleate (18:1
cis-Δ9) has been widely investigated, while very little data is available on the cell
damages caused by elaidate (18:1 trans-Δ9) and vaccenate (18:1 trans-Δ11), although
the potential health effects of these dietary trans fatty acids (TFAs) received great
publicity. We compared the effects of these four FAs on cell viability, apoptosis,
ER stress, JNK phosphorylation and autophagy as well as on ceramide and diglyceride
contents in RINm5F insulinoma cells. Similarly to oleate and unlike palmitate, TFAs
reduced cell viability only at higher concentration, and they had mild effects on
ER stress, apoptosis and autophagy. Palmitate increased ceramide and diglyceride levels
far more than any of the unsaturated fatty acids; however, incorporation of TFAs in
ceramides and diglycerides was strikingly more pronounced than that of oleate. This
indicates a correlation between the accumulation of lipid intermediates and the severity
of cell damage. Our findings reveal important metabolic characteristics of TFAs that
might underlie a long term toxicity and hence deserve further investigation.
