title: Leptin triggers Ca(2+) imbalance in monocytes of overweight subjects.
abstract: Obesity is a major risk factor in numerous diseases, in which elevated intracellular Ca(2+) plays a major role in increased adiposity. We examined the difference between Ca(2+) signals in monocytes of lean and overweight subjects and the relationship between leptin induced NADPH oxidase activation and intracellular calcium concentration [Ca(2+)](i) homeostasis. Our results are as follows: (1) The basal level of [Ca(2+)](i) in resting monocytes of overweight subjects (OW monocytes) was higher than that in control cells, whereas the leptin-induced peak of the Ca(2+) signal was lower and the return to basal level was delayed. (2) Ca(2+) signals were more pronounced in OW monocytes than in control cells. (3) Using different inhibitors of cellular signaling, we found that in control cells the Ca(2+) signals originated from intracellular pools, whereas in OW cells they were generated predominantly by Ca(2+)-influx from medium. Finally, we found correlation between leptin induced superoxide anion generation and Ca(2+) signals. The disturbed [Ca(2+)](i) homeostasis in OW monocytes was fully restored in the presence of fluvastatin. Statins have pleiotropic effects involving the inhibition of free radical generation that may account for its beneficial effect on elevated [Ca(2+)](i) and consequently on the pathomechanism of obesity.
authors.affiliation: First Department of Medicine, Medical and Health Science Center, University of Debrecen, Hungary.
authors.forename: János Tamás
authors.initials: JT
authors.lastname: Padra
authors.forename: Ildikó
authors.initials: I
authors.lastname: Seres
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fóris
authors.forename: György
authors.initials: G
authors.lastname: Paragh
authors.forename: Gabriella
authors.initials: G
authors.lastname: Kónya
authors.forename: György
authors.initials: G
authors.lastname: Paragh
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D050177:Overweight / Q000378:metabolism*
chemical_list: D020738:Leptin; D019255:NADPH Oxidases; D002118:Calcium