Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve.
Leptin, the product of the ob gene, plays a key role in the regulation of food intake via a cross-talk between hypothalamic leptin receptors and neuropeptides that affect feeding behaviour. Recent studies have shown a synergistic interaction between leptin and cholecystokinin (CCK) leading to suppression of food intake, which involves CCK-1 receptors and capsaicin-sensitive vagal fibres. In this study, we have investigated the presence of leptin receptors in afferent and efferent neurons of the vagus nerve. By using reverse transcription-polymerase chain reaction, mRNAs encoding long (Ob-Rb) and short (Ob-Ra) leptin receptor isoforms were detected in the rat nodose ganglion, which contains the cell bodies of the vagal afferent neurons. Western blot analysis confirmed the presence of leptin receptor-immunoreactive proteins in extracts from the vagal trunk. Immunohistochemistry showed the presence of leptin receptors and the leptin-induced transcription factor STAT3 in the cytoplasm of nodose ganglion cells. In cervical vagal segments, levels of leptin receptor protein displayed physiological regulation, with decreased amounts after feeding and increased levels after food restriction. In addition, leptin receptor and STAT3 immunoreactivities were detected in neurons of the nucleus of tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) by immunofluorescence histochemistry. Furthermore, direct double-labelling demonstrated colocalization of Ob-Rb and STAT3 immunoreactivities in cholinergic vagal efferent cell bodies of the DMNX. It is speculated that vagal leptin receptors, apart from being activated by adipocyte-derived leptin, may also be influenced by leptin produced by the stomach. This may explain the synergistic action of leptin and CCK on neuronal activity in the NTS and on food intake.
Buyse
M
M
Institut National de la Santé et de la Recherche Médicale U410, Faculté de Médecine Xavier Bichat, Paris, France.
Ovesjö
M L
ML
Goïot
H
H
Guilmeau
S
S
Péranzi
G
G
Moizo
L
L
Walker
F
F
Lewin
M J
MJ
Meister
B
B
Bado
A
A
D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004435:Eating / Q000502:physiology*; D004525:Efferent Pathways / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators