Triglyceride accumulation protects against fatty acid-induced lipotoxicity.
Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic beta-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.
Listenberger
Laura L
LL
Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110-1010, USA.
Han
Xianlin
X
Lewis
Sarah E
SE
Cases
Sylvaine
S
Farese
Robert V
RV
Ory
Daniel S
DS
Schaffer
Jean E
JE
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004351:Drug Resistance; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism / Q000633:toxicity*; D050356:Lipid Metabolism; D051379:Mice; D008954:Models, Biological; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism / Q000633:toxicity; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D014280:Triglycerides; D019301:Oleic Acid; D019308:Palmitic Acid; D044943:Fatty Acid Desaturases