Enhanced expression of leptin following acute gastric injury in rat.
Leptin, a product of ob-gene plays an important role in the regulation of food intake. Recently, leptin expression has been detected in gastric epithelium, but the physiologic role of gastric leptin remains unknown. The purpose of this study was: 1) to determine the effect of gastric injury by ethanol and aspirin on the expression of leptin in gastric mucosa and 2) to investigate whether exogenous leptin affects the integrity of gastric mucosa exposed to noxious agents such as ethanol or aspirin. In Wistar rats the acute gastric lesions were induced by intragastric application of 1.5 ml of 75% ethanol or acidified aspirin (100 mg/kg in 0.2 N HCl). Rats were divided into two groups and pretreated either with leptin (1-10 microg/kg i.p.) or vehicle (saline). Rats were anesthetized 1 h after i.g. induction of acute gastric lesions and the gastric blood flow (GBF) was measured by H2 gas clearance method. Then the rats were sacrificed, the stomach was excised and the mean lesions area was assessed by planimetry. In addition, mRNA and protein expression for leptin was analyzed in the gastric mucosa by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Both ethanol and acidified aspirin induced acute gastric lesions and led to significant reduction in GBF. In the intact gastric mucosa, the mRNA and protein expression for leptin was small but detectable. The exposure of gastric mucosa to noxious agents such as ethanol and aspirin was associated with markedly increased expression for gastric leptin at mRNA and protein level. Application of 75% ethanol or acidified aspirin caused wide-spread mucosal lesions. The pretreatment with exogenous leptin reduced dose-dependently these ethanol or aspirin-induced gastric lesions. The protective effects of exogenous leptin were accompanied by a significant attenuation of the fall of GBF. We conclude that: 1) Exogenous leptin exerts potent gastroprotective and hyperemic actions on gastric mucosa, and 2) Acute injury of gastric mucosa is associated with increased expression of leptin suggesting a possible role of this peptide in mediating of repair process in injured gastric mucosa.
Konturek
P C
PC
Department of Medicine I, University Erlangen-Nuremberg, Erlangen, Germany.
Brzozowski
T
T
Sulekova
Z
Z
Meixner
H
H
Hahn
E G
EG
Konturek
S J
SJ
D000818:Animals; D001241:Aspirin; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D020738:Leptin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control
D020738:Leptin; D012333:RNA, Messenger; D000431:Ethanol; D001241:Aspirin