The effect of polyunsaturated fatty acids on rat adipocyte lipogenesis: the role of protein kinase C, calcium and calmodulin.
Linolenic acid, a polyunsaturated fatty acid, has an insulin synergizing stimulatory effect on adipocyte lipogenesis. Since phorbol esters are also known to exert a similar effect through the activation of protein kinase C, and since they have fatty acid moieties, we investigated whether linolenic acid exerted its stimulatory effect through protein kinase C activation and whether calcium was involved in this mechanism. Our experiments show that H7, an inhibitor of protein kinase C; verapamil, a calcium blocker; and calmodulin inhibitors inhibited basal, insulin- and linolenic acid-stimulated lipogenesis. They also negated the insulin synergizing effect of linolenic acid. We conclude that linolenic acid, and possibly other unsaturated fatty acids, exert their stimulatory effect through stimulation of protein kinase C, calcium entry and calmodulin activation. These three processes are also important in maintaining basal lipogenesis.
Khokher
M A
MA
Department of Chemical Pathology, Royal Free Hospital, London, UK.
Dandona
P
P
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008042:Linolenic Acids / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology; D017962:alpha-Linolenic Acid
D002147:Calmodulin; D007328:Insulin; D007546:Isoquinolines; D008042:Linolenic Acids; D008055:Lipids; D010879:Piperazines; D017962:alpha-Linolenic Acid; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D011493:Protein Kinase C; D002118:Calcium