title: Okadaic acid decreases the leptin content in isolated mouse fat pads.
abstract: Okadaic acid (OA) decreased the leptin content in isolated mouse fat pads in a time and dose-dependent manner. MG-132, a membrane-permeable proteasome inhibitor, prevented the decrease by OA, suggesting the involvement of proteasome in the OA action. No significant decrease in the incorporation of [(3)H]leucine into leptin was observed with a 4-h incubation, although the amino acid incorporation was stimulated by insulin and decreased by cycloheximide. These results suggest that the OA action is independent of the decrease in protein synthesis. The proteasome fraction, which had been separated from the fat pads pretreated with OA, enhanced the proteolytic degradation of exogenous [(125)I]leptin in the presence of an ATP-regenerating system together with an ubiquitination system. No enhancement of hydrolytic activity against Suc-Leu-Leu-Val-Tyr-AMC was detected in the OA-treated proteasome fraction, suggesting that the activation of proteasome is not involved in the OA action. The OA-treated proteasome fraction had decreased phosphatase activity against p-nitrophenyl phosphate, suggesting that OA entering the cells may exert its action by preventing dephosphorylation of key molecules. OA may reduce the intracellular leptin content through the increased ubiquitination and proteolytic turnover of leptin by the proteasome, based on the decreased phosphatase activity.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 1 Gakuen-chou, Fukuyama, Hiroshima 729-0292, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mitsuishi
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshida
authors.forename: Toshio
authors.initials: T
authors.lastname: Motoyashiki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueki
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020738:Leptin / Q000378:metabolism*; D008297:Male; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D020738:Leptin; D019319:Okadaic Acid