Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression
N–6 polyunsaturated fatty acids (PUFA) suppress hepatic and adipocyte de novo lipogenesis by inhibiting the transcription of genes encoding key lipogenic proteins. In cultured 3T3-L1 adipocytes, arachidonic acid (20:4,n–6) suppression of lipogenic gene expression requires cyclooxygenase (COX) activi...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
1999-06-01
|
| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520335082 |
| _version_ | 1818606067764953088 |
|---|---|
| author | Michelle K. Mater Annette P. Thelen Donald B. Jump |
| author_facet | Michelle K. Mater Annette P. Thelen Donald B. Jump |
| author_sort | Michelle K. Mater |
| collection | DOAJ |
| description | N–6 polyunsaturated fatty acids (PUFA) suppress hepatic and adipocyte de novo lipogenesis by inhibiting the transcription of genes encoding key lipogenic proteins. In cultured 3T3-L1 adipocytes, arachidonic acid (20:4,n–6) suppression of lipogenic gene expression requires cyclooxygenase (COX) activity. In this study, we found no evidence to support a role for COX-1 or -2 in the 20:4,n–6 inhibition of hepatocyte lipogenic gene expression. In contrast to L1 preadipocytes, adipocytes and rat liver, RT-PCR and Western analyses did not detect COX-1 or COX-2 expression in cultured primary hepatocytes. Moreover, the COX inhibitor, flurbiprofen, did not affect the 20:4,n–6 regulation of lipogenic gene expression in primary hepatocytes. Despite the absence of COX-1 and -2 expression in primary hepatocytes, prostaglandins (PGE2 and PGF2α) suppressed fatty acid synthase, l-pyruvate kinase, and the S14 protein mRNA, while having no effect on acyl-CoA oxidase or CYP4A2 mRNA. Using PGE2 receptor agonist, the PGE2 effect on lipogenic gene expression was linked to EP3 receptors. PGE2 inhibited S14CAT activity in transfected primary hepatocytes and targeted the S14 PUFA-response region located –220 to –80 bp upstream from the transcription start site. Taken together, these studies show that COX-1 and COX-2 do not contribute to the n–6 PUFA suppression of hepatocyte lipogenic gene expression. However, cyclooxygenase products from non-parenchymal cells can act on parenchymal cells through a paracrine process and mimic the effects of n–6 PUFA on lipogenic gene expression.—Mater, M. K., A. P. Thelen, and D. B. Jump. Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression. J. Lipid Res. 1999. 40: 1045–1052. |
| first_indexed | 2024-12-16T14:04:58Z |
| format | Article |
| id | doaj.art-cb4d83722c1640f38751972a18033542 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T14:04:58Z |
| publishDate | 1999-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-cb4d83722c1640f38751972a180335422022-12-21T22:28:57ZengElsevierJournal of Lipid Research0022-22751999-06-0140610451052Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expressionMichelle K. Mater0Annette P. Thelen1Donald B. Jump2Departments of Physiology and Biochemistry, Michigan State University, East Lansing, MI 48824Departments of Physiology and Biochemistry, Michigan State University, East Lansing, MI 48824To whom correspondence should be addressed.; Departments of Physiology and Biochemistry, Michigan State University, East Lansing, MI 48824N–6 polyunsaturated fatty acids (PUFA) suppress hepatic and adipocyte de novo lipogenesis by inhibiting the transcription of genes encoding key lipogenic proteins. In cultured 3T3-L1 adipocytes, arachidonic acid (20:4,n–6) suppression of lipogenic gene expression requires cyclooxygenase (COX) activity. In this study, we found no evidence to support a role for COX-1 or -2 in the 20:4,n–6 inhibition of hepatocyte lipogenic gene expression. In contrast to L1 preadipocytes, adipocytes and rat liver, RT-PCR and Western analyses did not detect COX-1 or COX-2 expression in cultured primary hepatocytes. Moreover, the COX inhibitor, flurbiprofen, did not affect the 20:4,n–6 regulation of lipogenic gene expression in primary hepatocytes. Despite the absence of COX-1 and -2 expression in primary hepatocytes, prostaglandins (PGE2 and PGF2α) suppressed fatty acid synthase, l-pyruvate kinase, and the S14 protein mRNA, while having no effect on acyl-CoA oxidase or CYP4A2 mRNA. Using PGE2 receptor agonist, the PGE2 effect on lipogenic gene expression was linked to EP3 receptors. PGE2 inhibited S14CAT activity in transfected primary hepatocytes and targeted the S14 PUFA-response region located –220 to –80 bp upstream from the transcription start site. Taken together, these studies show that COX-1 and COX-2 do not contribute to the n–6 PUFA suppression of hepatocyte lipogenic gene expression. However, cyclooxygenase products from non-parenchymal cells can act on parenchymal cells through a paracrine process and mimic the effects of n–6 PUFA on lipogenic gene expression.—Mater, M. K., A. P. Thelen, and D. B. Jump. Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression. J. Lipid Res. 1999. 40: 1045–1052.http://www.sciencedirect.com/science/article/pii/S0022227520335082S14 proteinfatty acid synthasel-pyruvate kinasecyclooxygenasegene transcription |
| spellingShingle | Michelle K. Mater Annette P. Thelen Donald B. Jump Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression Journal of Lipid Research S14 protein fatty acid synthase l-pyruvate kinase cyclooxygenase gene transcription |
| title | Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression |
| title_full | Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression |
| title_fullStr | Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression |
| title_full_unstemmed | Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression |
| title_short | Arachidonic acid and PGE2 regulation of hepatic lipogenic gene expression |
| title_sort | arachidonic acid and pge2 regulation of hepatic lipogenic gene expression |
| topic | S14 protein fatty acid synthase l-pyruvate kinase cyclooxygenase gene transcription |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520335082 |
| work_keys_str_mv | AT michellekmater arachidonicacidandpge2regulationofhepaticlipogenicgeneexpression AT annettepthelen arachidonicacidandpge2regulationofhepaticlipogenicgeneexpression AT donaldbjump arachidonicacidandpge2regulationofhepaticlipogenicgeneexpression |