Analysis of the signal pathways involved in the regulation of fatty acid synthase gene expression by insulin and somatotropin.
Our previous studies have shown that somatotropin (ST) antagonizes insulin stimulation of fatty acid synthase (FAS) enzyme activity and gene transcription in adipocytes. In the present study, inhibitors of insulin and ST signaling pathways were used to dissect the mechanisms by which these hormones regulate FAS gene expression in 3T3-F442A adipocytes. Treating 3T3-F442A adipocytes with 10 microM PD98059, an inhibitor of mitogen-activated protein (MAP) kinase, did not affect the induction of FAS mRNA by insulin. When cells were cultured with H-89 (10 microM), GF109203X (10 microM), or staurosporine (100 nM), inhibitors of protein kinase A, protein kinase C, and Janus kinase (JAK) 2, respectively, the inhibitory effect of ST on FAS mRNA levels was not altered. However, H-89 significantly decreased the stimulatory effect of insulin on FAS mRNA abundance. Moreover, treatment with okadaic acid (1 microM), a serine/threonine phosphatase inhibitor, abolished the induction of FAS mRNA by insulin. These results suggest that serine/threonine dephosphorylation and protein kinase A-dependent pathways are involved in the regulation of FAS gene expression by insulin, but MAP kinase is probably not involved. Furthermore, our data indicate that protein kinase A, protein kinase C, and JAK2 do not mediate the effect of ST on regulation of FAS mRNA abundance.
Yin
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Department of Dairy and Animal Science, The Pennsylvania State University, University Park 16802, USA. yind@wadsworth.org
Griffin
M J
MJ
Etherton
T D
TD
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D064429:Fatty Acid Synthases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D013006:Growth Hormone / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D053614:Janus Kinase 2; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides
D007211:Indoles; D007328:Insulin; D007546:Isoquinolines; D008301:Maleimides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D013449:Sulfonamides; D013006:Growth Hormone; D064429:Fatty Acid Synthases; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D011493:Protein Kinase C; D019311:Staurosporine; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide