The concentration dependent biphasic effect of leptin on endogenous cholesterol synthesis in human monocytes

• Published in: Peptides (New York, N.Y. : 1980) Vol. 28; no. 10; pp. 2081 - 2083
• Main Authors: Balogh, Zoltán, Fóris, Gabriella, Kosztáczky, Béla, Paragh, György, Seres, Ildikó, Zsíros, Emese, Kónya, Gabriella
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2007; Elsevier Science
• Subjects: Biological and medical sciences; Cells, Cultured; Cholesterol - biosynthesis; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Hydroxymethylglutaryl CoA Reductases - drug effects; Leptin - pharmacology; Male; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Monocytes - drug effects; Monocytes - enzymology; Monocytes - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Vertebrates: endocrinology; Human; Endogenous; Monocyte; Leptin; Lipids; Biosynthesis; Adipokine; Cholesterol
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2007.07.004

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 [ 14C]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.