Epinephrine inhibits lipoprotein lipase gene expression in rat adipocytes through multiple steps in posttranscriptional processing.
Previous studies have demonstrated that in vitro treatment of adipocytes with catecholamines results in a decrease in the activity of the enzyme lipoprotein lipase (LPL). To examine the mechanism of this effect, primary cultures of rat adipocytes were cultured in the presence of various concentrations of epinephrine (10(-9)-10(-5) M). Epinephrine yielded a dose-dependent decrease in LPL activity; heparin-releasable LPL activity was reduced to 66% of control values after exposure to 10(-5) M epinephrine for 2 h. However, there was no effect of epinephrine on LPL immunoreactive mass, as measured by enzyme-linked immunosorbent assay. When cells were pulse labeled with [35S]methionine, there was a rapid and dose-dependent decrease in immunoprecipitable LPL. In spite of the decrease in LPL translation, neither epinephrine nor other catecholamines altered the level of LPL mRNA or the rate of LPL transcription. To further examine LPL posttranslational processing, cells were pulse labeled with [35S]methionine in the absence of epinephrine and then chased with unlabeled methionine in the presence of epinephrine. Cells exposed to epinephrine during the chase demonstrated a decrease in LPL secretion into the medium as well as a decrease in LPL degradation. The addition of epinephrine during LPL posttranslational processing did not alter the sensitivity of the newly synthesized LPL protein to endo-beta-N-acetylglucosaminidase-H. Thus, epinephrine had multiple effects on adipocyte LPL. Although there was a rapid decrease in LPL synthesis that was not due to changes in LPL mRNA, the level of LPL protein was unchanged under these conditions due to a decrease in LPL degradation and secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Ong
J M
JM
Department of Medicine/Division of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, California 90048.
Saffari
B
B
Simsolo
R B
RB
Kern
P A
PA
D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology; D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000502:physiology
D012333:RNA, Messenger; D008071:Lipoprotein Lipase; D004837:Epinephrine