Insulin, glucagon and fatty acid treatment of hepatocytes does not result in phosphorylation or changes in activity of triacylglycerol hydrolase.
It is recognized that the majority of very low density lipoprotein (VLDL) associated triacylglycerol (TG) is synthesized from fatty acids and partial acylglycerols generated by lipolysis of intra-hepatic storage rather than made de novo. Triacylglycerol hydrolase (TGH) is involved in mobilizing stored TG. Modulating the ability of TGH to hydrolyze stored lipids represents a potentially regulated and rate limiting step in VLDL assembly. Phosphorylation of lipases and carboxylesterases trigger diverse but functionally significant events. We explored the potential for regulating the mobilization of hepatic TG through phosphorylation of TGH. Insulin is known to suppress VLDL secretion from liver, and glucagon can be considered an opposing hormone. However, neither insulin nor glucagon treatment of hepatocytes led to phosphorylation of TGH or changes in its activity. Augmenting intracellular TG stores by incubations with oleic acid also did not lead to changes in TGH activity. Therefore, changes in phosphorylation state are not a mechanism for regulating TGH activity, access to TG substrate pools or for TGH-mediated contributions to VLDL assembly and secretion.
Gilham
Dean
D
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Perreault
Kathleen R
KR
Holmes
Charles F B
CF
Brindley
David N
DN
Vance
Dennis E
DE
Lehner
Richard
R
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007328:Insulin / Q000494:pharmacology*; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D019301:Oleic Acid; D005934:Glucagon; D020928:Mitogen-Activated Protein Kinases; D008049:Lipase; D000469:Alkaline Phosphatase; D010749:Phosphoprotein Phosphatases