Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2011-09-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520408557 |
| _version_ | 1818658506535862272 |
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| author | Jorge Matias Caviglia Constance Gayet Tsuguhito Ota Antonio Hernandez-Ono Donna M. Conlon Hongfeng Jiang Edward A. Fisher Henry N. Ginsberg |
| author_facet | Jorge Matias Caviglia Constance Gayet Tsuguhito Ota Antonio Hernandez-Ono Donna M. Conlon Hongfeng Jiang Edward A. Fisher Henry N. Ginsberg |
| author_sort | Jorge Matias Caviglia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T03:58:27Z |
| format | Article |
| id | doaj.art-ecd86f22b7584989a33ca87a26a4b867 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T03:58:27Z |
| publishDate | 2011-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-ecd86f22b7584989a33ca87a26a4b8672022-12-21T22:04:34ZengElsevierJournal of Lipid Research0022-22752011-09-0152916361651Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagyJorge Matias Caviglia0Constance Gayet1Tsuguhito Ota2Antonio Hernandez-Ono3Donna M. Conlon4Hongfeng Jiang5Edward A. Fisher6Henry N. Ginsberg7Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NYDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NYDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NYDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NYDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NYDepartment of Medicine, Columbia University College of Physicians and Surgeons, New York, NYDepartments of Medicine, New York University School of Medicine, New York, NY; Cell Biology, New York University School of Medicine, New York, NYTo whom correspondence should be addressed; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY; To whom correspondence should be addressedAlthough 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.http://www.sciencedirect.com/science/article/pii/S0022227520408557apolipoproteinendoplasmic reticulumoleic acidpalmitic aciddocosahexaenoic acidhepatoctyes |
| spellingShingle | Jorge Matias Caviglia Constance Gayet Tsuguhito Ota Antonio Hernandez-Ono Donna M. Conlon Hongfeng Jiang Edward A. Fisher Henry N. Ginsberg Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy Journal of Lipid Research apolipoprotein endoplasmic reticulum oleic acid palmitic acid docosahexaenoic acid hepatoctyes |
| title | Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy |
| title_full | Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy |
| title_fullStr | Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy |
| title_full_unstemmed | Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy |
| title_short | Different fatty acids inhibit apoB100 secretion by different pathways: unique roles for ER stress, ceramide, and autophagy |
| title_sort | different fatty acids inhibit apob100 secretion by different pathways unique roles for er stress ceramide and autophagy |
| topic | apolipoprotein endoplasmic reticulum oleic acid palmitic acid docosahexaenoic acid hepatoctyes |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520408557 |
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