Molecular and Cellular Biochemistry

, Volume 303, Issue 1–2, pp 105–113 | Cite as

Saturated fatty acid-mediated endoplasmic reticulum stress and apoptosis are augmented by trans-10, cis-12-conjugated linoleic acid in liver cells

  • Yuren Wei
  • Dong Wang
  • Michael J. Pagliassotti


Lipid accumulation in non-adipose tissues leads to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Recent evidence suggests that lipotoxicity in hepatocytes involves endoplasmic reticulum (ER) stress and c-Jun NH2-terminal kinase-mediated apoptosis. The present study examined (1) the dose–response and time course characteristics of fatty acid-mediated ER stress and apoptosis in H4IIE liver cells; (2) whether saturated fatty acid-induced apoptosis involved the ER-associated caspase-12; and (3) whether trans-10, cis-12-conjugated linoleic acid, an inhibitor of stearoyl-CoA desaturase, influenced fatty acid-mediated ER stress and apoptosis. Saturated fatty acids induced ER stress in a dose-dependent manner with a time course that was delayed relative to chemical-induction of ER stress. Saturated fatty acids increased caspase-9 and caspase-3 activity, however increased caspase-12 activity was not observed. Inhibition of stearoyl-CoA desaturase, using conjugated linoleic acid (trans-10, cis-12), augmented saturated fatty acid-induced ER stress and apoptosis. These data suggest that saturated fatty acids induce ER stress and apoptosis at physiologic concentrations and with a relatively rapid time course. It would appear that saturated fatty acid-mediated apoptosis occurs independently of caspase-12 activation. Since conjugated linoleic acid inhibited stearoyl-CoA desaturase activity, it is hypothesized that saturation, per se, plays a role in lipotoxicity in liver cells.


Lipotoxicity Non-alcoholic fatty liver disease Apoptosis 



This work was supported by National Institutes of Diabetes and Digestive and Kidney Diseases grant DK-072017.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Yuren Wei
    • 1
  • Dong Wang
    • 1
  • Michael J. Pagliassotti
    • 1
  1. 1.Department of Food Science and Human NutritionColorado State UniversityFort CollinsUSA

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