Triglyceride accumulation protects against fatty acid-induced lipotoxicity

Laura L. Listenberger, Xianlin Han, Sarah E. Lewis, Sylvaine Cases, Robert V. Farese, Daniel S. Ory, Jean E. Schaffer

Research output: Contribution to journalArticlepeer-review

1388 Scopus citations


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.

Original languageEnglish
Pages (from-to)3077-3082
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
StatePublished - Mar 18 2003


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