Arachidonic acid inhibits lipogenic gene expression in 3T3-L1 adipocytes through a prostanoid pathway.
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.
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Department of Physiology, Michigan State University, East Lansing 48824, USA.
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D016475:3T3 Cells; D000199:Actins / Q000235:genetics; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology*; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000199:Actins; D016861:Cyclooxygenase Inhibitors; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D012333:RNA, Messenger; D014280:Triglycerides; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D019301:Oleic Acid; D003907:Dexamethasone; D015118:Eicosapentaenoic Acid; D015237:Dinoprost; D015500:Chloramphenicol O-Acetyltransferase; D037342:Pertussis Toxin; D015232:Dinoprostone