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Effects of interactions between interleukin-1 beta and leptin on cat intestinal vagal mechanoreceptors
Stéphanie Gaigé1, Einate Abou, Anne Abysique
1Laboratoire de Physiologie Neurovégétative (UMR CNRS 6153, UMR INRA 1147), Faculté des Sciences et Techniques Saint-Jérôme, Université Aix-Marseille 3, Cases postales 351-352, Avenue Escadrille Normandie Niemen, 13397 Marseille Cedex 20, France.
Insights
Leptin influences intestinal mechanoreceptors through interleukin-1beta (IL-1β) in some nerve pathways, but not others. This reveals distinct roles for these pathways in signaling digestion and inflammation to the brain.
Area of Science:
- Neuroscience
- Gastroenterology
- Immunology
Background:
- Previous research established leptin's action on intestinal vagal mechanoreceptors, with effects modulated by interleukin-1beta receptor antagonist (IL-1ra).
- The precise role of interleukin-1beta (IL-1β) in mediating leptin's effects on these receptors remained unclear.
Purpose of the Study:
- To elucidate the involvement of IL-1β in leptin's action on intestinal vagal mechanoreceptors.
- To differentiate between leptin-sensitive and insensitive vagal afferent pathways based on IL-1β sensitivity.
Main Methods:
- Recording single vagal afferent activities from intestinal mechanoreceptors in anesthetized cats via nodose ganglion microelectrode implantation.
- Administering IL-1β and cholecystokinin (CCK) into the superior mesenteric artery to observe effects on leptin-activated (type 1) and leptin-inhibited (type 2) units.
- Utilizing IL-1ra pre-treatment to block IL-1β and leptin effects.
Main Results:
- IL-1β activated both leptin-activated (type 1) and leptin-inhibited (type 2) units, suggesting IL-1β sensitivity in both populations.
- CCK activated only IL-1β-sensitive units; subsequent IL-1β administration enhanced type 1 unit activation but abolished type 2 unit activation.
- IL-1ra pre-treatment blocked IL-1β effects and leptin's excitatory effects on type 1 units, while enhancing leptin's inhibitory effects on type 2 units.
Conclusions:
- Leptin acts on intestinal vagal mechanoreceptors via IL-1β for type 1 units and independently of IL-1β for type 2 units.
- Type 1 and type 2 units represent distinct vagal afferent populations.
- These distinct pathways transmit differential information regarding ingestion or inflammation to the central nervous system based on the chemical milieu.
Abstract:
In a previous study, we established that leptin acts on chemosensitive intestinal vagal mechanoreceptors and that its excitatory effects are blocked by the endogenous interleukin-1beta receptor antagonist (Il-1ra). To determine how interleukin-1beta (Il-1beta) is involved in the action of leptin, we studied the effects of this drug on the single vagal afferent activities of intestinal mechanoreceptors in anaesthetized cats. For this purpose, the activity of 34 intestinal vagal mechanoreceptors was recorded via glass microelectrodes implanted in the nodose ganglion. Il-1beta (1 microg) administered into the artery irrigating the upper part of the intestine activated both the 16 leptin-activated units (type 1 units; P < 0.01) and the 12 leptin-inhibited units (type 2 units; P < 0.001), but had no effect on the six leptin-insensitive units. Cholecystokinin (CCK, 10 microg) induced an activatory response only in the two types of Il-1beta-sensitive units. When Il-1beta was administered after CCK, its excitatory effects on type 1 units were enhanced, whereas the excitatory effects on type 2 units were abolished. Pre-treatment with Il-1ra (250 microg) blocked all the effects of Il-1beta and the excitatory effects of leptin on type 1 units, whereas it enhanced the inhibitory effects of leptin on type 2 units. It can therefore be concluded that (i) leptin acts on intestinal vagal mechanoreceptors via Il-1beta in the case of the type 1 units and independently of Il-1beta in the case of the type 2 units, and (ii) type 1 and type 2 units belong to two different populations of vagal afferents that transmit different information about ingestion or inflammation to the CNS, depending on the chemical environment.
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