title: Gastroprotection and control of food intake by leptin. Comparison with cholecystokinin and prostaglandins.
abstract: Circulating peptide leptin which is the product of the ob gene is known to provide feedback information on the size of fat stores to central OB-receptors that control food intake. Recently, leptin messenger RNA and leptin protein have been detected in gastric epithelium and leptin was found to be released by CCK into circulation but the physiological role of this gastric leptin remains unknown. As CCK has been reported to protect gastric mucosa against various noxious agents, we designed the study to determine the influence of leptin and CCK on the gastroprotection and the control of food intake and to compare them with classic gastroprotective substance, prostaglandin E2, in rats with acute gastric mucosal lesions induced by topical application of 75% ethanol. Four series of Wistar rats (A, B, C and D) were used to determine; A) the effects of various doses of leptin (0.1-10 microg/kg) given intraperitoneally (i.p.) on ethanol-induced gastric lesions, gastric blood flow (GBF) and plasma levels of immunoreactive leptin; B) the effects of various doses of CCK-8 (0.1-10 microg/kg i.p.) on ethanol-induced gastric lesions, GBF and plasma levels of leptin; C) the effects of various doses of PGE2 (12.5--100 microg/kg) given intragastrically (i.g.) on ethanol-induced gastric lesions and GBF and D) the influence of leptin, CCK and PGE2 on the intake of liquid meal in rats. Rats were anesthetized with ether 1 h after i.g. administration of 75% ethanol to measure the GBF using H2-gas clearance technique and blood samples were withdrawn for the measurement of plasma leptin levels by radioimmunoassay (RIA). Food intake was assessed in separate group of rats fasted 18 h and then fed with liquid caloric meal. Leptin, CCK and PGE2 reduced dose-dependently gastric lesions induced by 75% ethanol, the dose reducing these lesions by 50% (ED50) being, respectively, 1 microg/kg, 5 microg/kg and 20 microg/kg. The protective effects of leptin, CCK-8 and PGE2 were accompanied by significant attenuation of the fall of the GBF caused by ethanol. Leptin and CCK reduced also dose-dependently the food intake while PGE2 was not effective. Leptin and CCK resulted a dose-dependent increment in the plasma leptin levels. We conclude that: 1) exogenous leptin and CCK, causing similar increments in plasma immunoreactive leptin levels, protect dose-dependently gastric mucosa against the damage provoked by 75% ethanol; 2) Leptin and CCK afford similar gastroprotective activity to that attained with PGE2 but unlike PGE2 were highly effective in the reduction in food intake and 3) the protective effects of leptin, CCK and PGE2 were accompanied by significant increase of GBF suggesting that the protection afforded by these substances are mediated, at least in part, by gastric hyperemia.
authors: Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
authors: P C
authors: PC
authors: Konturek
authors: S J
authors: SJ
authors: Konturek
authors: T
authors: T
authors: Brzozowski
authors: E G
authors: EG
authors: Hahn
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004064:Digestive System / Q000098:blood supply / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000378:metabolism; D020738:Leptin; D008297:Male; D009765:Obesity; D011453:Prostaglandins / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020738:Leptin; D011453:Prostaglandins; D011506:Proteins; D000431:Ethanol; D002766:Cholecystokinin; D015232:Dinoprostone