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

Content Provider	Springer Nature Link
Author	Wei, Yuren Wang, Dong Pagliassotti, Michael J.
Copyright Year	2007
Abstract	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 NH$_{2}$-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.
Starting Page	105
Ending Page	113
Page Count	9
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	303
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2007-04-11
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Lipotoxicity Non-alcoholic fatty liver disease Apoptosis Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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