Triglyceride accumulation protects against fatty acid-induced lipotoxicity

LL Listenberger, X Han, SE Lewis… - Proceedings of the …, 2003 - National Acad Sciences
LL Listenberger, X Han, SE Lewis, S Cases, RV Farese Jr, DS Ory, JE Schaffer
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
Excess lipid accumulation in non-adipose tissues is associated with insulin resistance,
pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the
relative toxicity of two common dietary long chain fatty acids is related to channeling of these
lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride
accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into
triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced …
Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis. Moreover, in the setting of impaired triglyceride synthesis, oleate induces lipotoxicity. Our findings support a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation.
National Acad Sciences