Antral mucosa expresses functional leptin receptors coupled to STAT-3 signaling, which is involved in the control of gastric secretions in the rat.
OBJECTIVE
Leptin is a circulating hormone that communicates the peripheral nutritional status to the hypothalamus, which controls food intake, energy expenditure, and body weight. This study characterizes leptin receptors and leptin-sensitive STAT proteins in the antrum and investigates the effects of leptin on gastric secretions.


METHODS
The effects of leptin on gastrin messenger RNA (mRNA), plasma gastrin, gastric acid in vivo in the rat, and on somatostatin and gastrin secretions by isolated antral cells were determined in vitro. Leptin receptors were investigated in isolated rat antral cells by reverse transcription-polymerase chain reaction and binding of [(125)I]-leptin studies. The effects of in vivo and in vitro leptin on transduction signal STAT proteins were investigated by immunoblotting antral extracts.


RESULTS
Peripheral injection of leptin inhibited in a dose-dependent manner, basal gastric secretion, gastrinemia, and mucosal gastrin mRNA in vivo. mRNAs encoding the long (Ob-Rb) and short (Ob-Ra) receptor forms were detected in rat antral mucosa, as were STAT-1, -3, and -5b immunoreactive proteins. Isolated antral cells specifically bound [(125)I]-leptin, and addition of leptin to these cells inhibited the release of somatostatin and increased the release of gastrin. These effects were associated with an increase in nuclear STAT-3 proteins in vitro and in vivo.


CONCLUSIONS
This study provides the first molecular evidence for the coexpression of leptin receptors and STAT-3 in antral mucosa. It provides further evidence for the involvement of leptin in the control of gastric secretions.
Goïot
H
H
INSERM Unité 410, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75870 Paris Cedex 18, France.
Attoub
S
S
Kermorgant
S
S
Laigneau
J P
JP
Lardeux
B
B
Lehy
T
T
Lewin
M J
MJ
Bado
A
A
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008894:Milk Proteins; D011706:Pyloric Antrum; D012333:RNA, Messenger / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005755:Gastrins; D020738:Leptin; D008894:Milk Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494081:Stat1 protein, rat; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; C515447:leptin receptor, mouse; D013004:Somatostatin