Document Detail

Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy.
MedLine Citation:
PMID:  21719579     Owner:  NLM     Status:  MEDLINE    
Although short-term incubation of hepatocytes with oleic acid (OA) stimulates secretion of apolipoprotein B100 (apoB100), exposure to higher doses of OA for longer periods inhibits secretion in association with induction of endoplasmic reticulum (ER) stress. Palmitic acid (PA) induces ER stress, but its effects on apoB100 secretion are unclear. Docosahexaenoic acid (DHA) inhibits apoB100 secretion, but its effects on ER stress have not been studied. We compared the effects of each of these fatty acids on ER stress and apoB100 secretion in McArdle RH7777 (McA) cells: OA and PA induced ER stress and inhibited apoB100 secretion at higher doses; PA was more potent because it also increased the synthesis of ceramide. DHA did not induce ER stress but was the most potent inhibitor of apoB100 secretion, acting via stimulation of autophagy. These unique effects of each fatty acid were confirmed when they were infused into C57BL6J mice. Our results suggest that when both increased hepatic secretion of VLDL apoB100 and hepatic steatosis coexist, reducing ER stress might alleviate hepatic steatosis but at the expense of increased VLDL secretion. In contrast, increasing autophagy might reduce VLDL secretion without causing steatosis.
Jorge Matias Caviglia; Constance Gayet; Tsuguhito Ota; Antonio Hernandez-Ono; Donna M Conlon; Hongfeng Jiang; Edward A Fisher; Henry N Ginsberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-30
Journal Detail:
Title:  Journal of lipid research     Volume:  52     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-15     Completed Date:  2012-02-24     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1636-51     Citation Subset:  IM    
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
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MeSH Terms
Apolipoprotein B-100 / secretion*
Autophagy / drug effects*
Cell Line
Ceramides / metabolism*
Endoplasmic Reticulum / drug effects*,  metabolism
Fatty Acids / chemistry,  pharmacology*
Fatty Acids, Monounsaturated / pharmacology
Liver / cytology,  drug effects,  metabolism
Mice, Inbred C57BL
Oxidative Stress / drug effects*
Phenylbutyrates / pharmacology
Stearoyl-CoA Desaturase / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Apolipoprotein B-100; 0/Ceramides; 0/Fatty Acids; 0/Fatty Acids, Monounsaturated; 0/Phenylbutyrates; 35891-70-4/thermozymocidin; 7WY7YBI87E/4-phenylbutyric acid; EC protein, mouse; EC Desaturase

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