Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis
Adiponectin receptors play a key role in steatosis and inflammation; however, very little is known about regulation of adiponectin receptors in liver. Here, we examined the effects of palmitate loading, endoplasmic reticulum (ER) stress, and the hypolipidemic agent fenofibrate on adiponectin recepto...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520306854 |
| _version_ | 1819293495304650752 |
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| author | Shaikh Mizanoor Rahman Ishtiaq Qadri Rachel C. Janssen Jacob E. Friedman |
| author_facet | Shaikh Mizanoor Rahman Ishtiaq Qadri Rachel C. Janssen Jacob E. Friedman |
| author_sort | Shaikh Mizanoor Rahman |
| collection | DOAJ |
| description | Adiponectin receptors play a key role in steatosis and inflammation; however, very little is known about regulation of adiponectin receptors in liver. Here, we examined the effects of palmitate loading, endoplasmic reticulum (ER) stress, and the hypolipidemic agent fenofibrate on adiponectin receptor R2 (AdipoR2) levels and AMP-activated protein kinase (AMPK) in human hepatoma Huh7 cells and in Huh.8 cells, a model of hepatitis C-induced steatosis. Palmitate treatment reduced AdipoR2 protein and basal AMPK phosphorylation in Huh7 cells. Fenofibrate treatment preserved AdipoR2 and phosphorylated AMPK (pAMPK) levels in palmitate-treated cells accompanied by reduced triglyceride (TG) accumulation and less activation of ER stress markers CCAAT/enhancer binding (C/EBPβ) and eukaryotic translation initiation factor 2 α. ER stress agents thapsigargin and tunicamycin suppressed AdipoR2 and pAMPK levels in Huh7 cells, while fenofibrate and the chemical chaperone 4-phenylbutyrate (PBA) prevented these changes. AdipoR2 levels were lower in Huh.8 cells and fenofibrate treatment increased AdipoR2 while reducing activation of c-Jun N-terminal kinase and C/EBPβ expression without changing TG levels. Taken together, these results suggest that fatty acids and ER stress reduce AdipoR2 protein and pAMPK levels, while fenofibrate and PBA might be important therapeutic agents to correct lipid- and ER stress-mediated loss of AdipoR2 and pAMPK associated with nonalcoholic steatohepatitis. |
| first_indexed | 2024-12-24T04:11:20Z |
| format | Article |
| id | doaj.art-92c6b8883cf9405eac07a70e1e8df7fc |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-24T04:11:20Z |
| publishDate | 2009-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-92c6b8883cf9405eac07a70e1e8df7fc2022-12-21T17:16:03ZengElsevierJournal of Lipid Research0022-22752009-11-01501121932202Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosisShaikh Mizanoor Rahman0Ishtiaq Qadri1Rachel C. Janssen2Jacob E. Friedman3To whom correspondence should be addressed; Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045; Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO 80045Adiponectin receptors play a key role in steatosis and inflammation; however, very little is known about regulation of adiponectin receptors in liver. Here, we examined the effects of palmitate loading, endoplasmic reticulum (ER) stress, and the hypolipidemic agent fenofibrate on adiponectin receptor R2 (AdipoR2) levels and AMP-activated protein kinase (AMPK) in human hepatoma Huh7 cells and in Huh.8 cells, a model of hepatitis C-induced steatosis. Palmitate treatment reduced AdipoR2 protein and basal AMPK phosphorylation in Huh7 cells. Fenofibrate treatment preserved AdipoR2 and phosphorylated AMPK (pAMPK) levels in palmitate-treated cells accompanied by reduced triglyceride (TG) accumulation and less activation of ER stress markers CCAAT/enhancer binding (C/EBPβ) and eukaryotic translation initiation factor 2 α. ER stress agents thapsigargin and tunicamycin suppressed AdipoR2 and pAMPK levels in Huh7 cells, while fenofibrate and the chemical chaperone 4-phenylbutyrate (PBA) prevented these changes. AdipoR2 levels were lower in Huh.8 cells and fenofibrate treatment increased AdipoR2 while reducing activation of c-Jun N-terminal kinase and C/EBPβ expression without changing TG levels. Taken together, these results suggest that fatty acids and ER stress reduce AdipoR2 protein and pAMPK levels, while fenofibrate and PBA might be important therapeutic agents to correct lipid- and ER stress-mediated loss of AdipoR2 and pAMPK associated with nonalcoholic steatohepatitis.http://www.sciencedirect.com/science/article/pii/S0022227520306854insulin resistanceinflammationsignal transductiondiabetesobesitypalmitate |
| spellingShingle | Shaikh Mizanoor Rahman Ishtiaq Qadri Rachel C. Janssen Jacob E. Friedman Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis Journal of Lipid Research insulin resistance inflammation signal transduction diabetes obesity palmitate |
| title | Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis |
| title_full | Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis |
| title_fullStr | Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis |
| title_full_unstemmed | Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis |
| title_short | Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis |
| title_sort | fenofibrate and pba prevent fatty acid induced loss of adiponectin receptor and pampk in human hepatoma cells and in hepatitis c virus induced steatosis |
| topic | insulin resistance inflammation signal transduction diabetes obesity palmitate |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520306854 |
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