Title | Arachidonic acid inhibits lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway. |
Publication Type | Journal Article |
Year of Publication | 1998 |
Authors | Mater, MK, Pan, D, Bergen, WG, Jump, DB |
Journal | J Lipid Res |
Volume | 39 |
Issue | 7 |
Pagination | 1327-34 |
Date Published | 1998 Jul |
ISSN | 0022-2275 |
Keywords | 3T3 Cells, Actins, Adipocytes, Animals, Arachidonic Acid, Chloramphenicol O-Acetyltransferase, Cyclooxygenase Inhibitors, Dexamethasone, Dinoprost, Dinoprostone, Eicosapentaenoic Acid, Fatty Acids, Nonesterified, Fatty Acids, Unsaturated, Gene Expression Regulation, Mice, Oleic Acid, Pertussis Toxin, Prostaglandins, RNA, Messenger, Signal Transduction, Transcription, Genetic, Transfection, Triglycerides, Virulence Factors, Bordetella |
Abstract | This report examines the effect of polyunsaturated fatty acids (PUFA) on lipogenic gene expression in cultured 3T3-L1 adipocytes. Arachidonic acid (20:4, n-6) and eicosapentaenoic acid (20:5, n-3) suppressed mRNAs encoding fatty acid synthase (FAS) and S14, but had no effect on beta-actin. Using a clonal adipocyte cell line containing a stably integrated S14CAT fusion gene, oleic acid (18:1, n-9), arachidonic acid (20:4, n-6) and eicosapentaenoic acid (20:5, n-3) inhibited chloramphenicol acetyltransferase (CAT) activity with an ED50 of 800, 50, and 400 microM, respectively. Given the high potency of 20:4, n-6, its effect on adipocyte gene expression was characterized. Arachidonic acid suppressed basal CAT activity, but did not affect glucocorticoid-mediated induction of S14CAT expression. The effect of 20:4, n-6 on S14CAT expression was blocked by an inhibitor of cyclooxygenase implicating involvement of prostanoids. Prostaglandins (PGE2 and PGF2alpha at 10 microM) inhibited CAT activity through a pertussis toxin-sensitive Gi/Go-coupled signalling cascade. Our results suggest that 20:4, n-6 inhibits lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway. This mechanism of control differs from the polyunsaturated fatty acid-mediated suppression of hepatic lipogenic gene expression. |
Alternate Journal | J. Lipid Res. |
PubMed ID | 9684735 |
Grant List | R01 DK043220 / DK / NIDDK NIH HHS / United States DK43220 / DK / NIDDK NIH HHS / United States |