title: Obesity abrogates the concentration-dependent effect of leptin on endogenous cholesterol synthesis in human monocytes.
abstract: Leptin the cytokine-like hormone is involved not only in local inflammations, but it regulates cholesterol biosynthesis in human monocytes. Since, monocyte-membrane composition in obesity shows considerable difference from control cells, our aim was to elucidate the concentration dependence of the effect of leptin in OW monocytes, and the downstream signaling of high and low leptin concentrations. Control and OW monocytes were stimulated with leptin in the presence or absence of different inhibitors. Our results are as follows: a concentration-dependent biphasic effect could only be detected in control monocytes whereas in OW cells only elevated cholesterol synthesis was found. The signal pathway of 50 ng/mL leptin stimulation involves Ca(2+) signal, activation of PI3K, MAPK and HMG CoA reductase. In the 500 ng/mL leptin-stimulated control monocytes the suppression of cholesterol synthesis was dependent on the Ca(2+) signal, the H-7 sensitive cPKC and PI3K activation, whereas in OW monocytes only PI3K was involved in increased cholesterol synthesis. We conclude that leptin-signaling in OW monocytes is characterized by Ca(2+) influx, abrogation of H-7 sensitive cPKC activation, and by PI3K mediated PKC activation.
authors: First Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors: Zoltán
authors: Z
authors: Balogh
authors: Gabriella
authors: G
authors: Fóris
authors: Gabriella
authors: G
authors: Kónya
authors: György
authors: G
authors: Paragh
authors: Tamás
authors: T
authors: Köbling
authors: János T
authors: JT
authors: Padra
authors: Zsolt
authors: Z
authors: Sarang
authors: György
authors: G
authors: Paragh
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000328:Adult; D002118:Calcium; D002784:Cholesterol / Q000096:biosynthesis*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020738:Leptin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D058539:Phosphatidylinositol 3-Kinase; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium