Comparison of the effect of individual saturated and unsaturated fatty acids on cell growth and death induction in the human pancreatic beta-cell line NES2Y.
We tested the effects of various types of fatty acids, differing in the degree of saturation and in the cis/trans configuration of the double bond, on the growth and viability of NES2Y cells (a human pancreatic beta-cell line). We found that during a 48-hour incubation period, saturated fatty acids, i.e. palmitic and stearic acids, at a physiologically relevant concentration of 1 mM and higher concentrations induced death of the beta-cells while their counterpart unsaturated fatty acids, i.e. palmitoleic and oleic acids, did not induce cell death at concentrations up to 3 mM. We also found that unsaturated elaidic acid with a trans double bond exerted significant inhibition of growth of the beta-cells at a concentration approximately ten times lower, i.e. 0.1 mM vs. 1 mM, than counterpart oleic acid with a cis double bond. This is the first direct evidence that a trans unsaturated fatty acid is significantly more effective in inhibiting beta-cell growth than a counterpart cis unsaturated fatty acid. Furthermore, we newly demonstrated that beta-cell death induced by saturated fatty acids is related to significant increase of caspase-2 activity (2 to 5-fold increase) but not to caspase-3 activation. The growth-inhibiting effect of saturated fatty acids at concentrations lower than death-inducing concentrations correlates with certain increase of caspase-2 activity.
Fürstova
Vlasta
V
Division of Cell and Molecular Biology & Center for Research of Diabetes, Metabolism and Nutrition, 3rd Faculty of Medicine, Charles University in Prague, Ruska 87, 100 00 Prague 10, Czech Republic.
Kopska
Tereza
T
James
Roger F L
RF
Kovar
Jan
J
D053143:Caspase 2 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D016895:Culture Media, Serum-Free; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D053143:Caspase 2; D053148:Caspase 3