The concentration dependent biphasic effect of leptin on endogenous cholesterol synthesis in human monocytes.
In human monocytes 100 ng/mL leptin increased both statin-inhibitable free radical and cholesterol production in vitro. In our recent study, we aimed to elucidate the concentration dependence of observed leptin-effect. Following leptin stimulation cholesterol synthesis was measured in the presence of inhibitors to determine affected signal pathways. Leptin at low (10-100 ng/mL) concentrations increased [(14)C]acetate incorporation, whereas at 250 ng/mL and higher concentrations it suppressed cholesterol synthesis. HMG CoA reductase, phosphatidyl-3-kinase (PI3K) and mitogen activated protein kinase (MAPK) were involved in mediating leptin effects at low concentrations, whereas the cholesterol synthesis suppression was abolished by inhibitors of protein kinase C (PKC) and PI3K.
Balogh
Zoltán
Z
First Department of Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen H-4012, Hungary.
Fóris
Gabriella
G
Kosztáczky
Béla
B
Paragh
György
G
Seres
Ildikó
I
Zsíros
Emese
E
Kónya
Gabriella
G
Paragh
György
G
D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors
D004791:Enzyme Inhibitors; D020738:Leptin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D020928:Mitogen-Activated Protein Kinases