Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats

Wang, Yu Hua; Taché, Y.; Sheibel, A. B.; Go, Vay Liang W.; Wei, Jiann-Wu

doi:10.1152/ajpregu.1997.273.2.r833

Cited by 106 publications

(114 citation statements)

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“…These observations are consistent with leptin plus CCK interaction involving activation of CCK-A receptors located in visceral capsaicin-sensitive afferents, most likely of vagal origin. This is further supported by recent electrophysiological recordings in an isolated vagusstomach preparation in rats showing an increased responsiveness of gastric vagal afferents to leptin by pretreatment with CCK (27).…”

Section: Discussionsupporting

confidence: 67%

“…There is also evidence of synergistic interaction between peripheral CCK and other hormones released postprandially such as insulin and glucagon in rats (25,26). Recently, we observed in an in vitro vagus-stomach preparation that CCK increases responsiveness of vagal afferents to leptin as assessed electrophysiologically (27). Therefore, in the present study we investigate the potential functional synergistic interaction between peripheral leptin and CCK in the short-term modulation of food intake in lean mice.…”

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confidence: 91%

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Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Barrachina

Martı́nez

Wang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

405

256

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Leptin is a circulating protein involved in the long-term regulation of food intake and body weight. Cholecystokinin (CCK) is released postprandially and elicits satiety signals. We investigated the interaction between leptin and CCK-8 in the short-term regulation of food intake induced by 24-hr fasting in lean mice. Leptin, injected intraperitoneally (i.p.) at low doses (4-120 g͞kg), which did not influence feeding behavior for the first 3 hr postinjection, decreased food intake dose dependently by 47-83% during the first hour when coinjected with a subthreshold dose of CCK. Such an interaction was not observed between leptin and bombesin. The food-reducing effect of leptin injected with CCK was not associated with alterations in gastric emptying or locomotor behavior. Leptin-CCK action was blocked by systemic capsaicin at a dose inducing functional ablation of sensory afferent fibers and by devazepide, a CCK-A receptor antagonist but not by the CCK-B receptor antagonist, L-365,260. The decrease in food intake which occurs 5 hr after i.p. injection of leptin alone was also blunted by devazepide. Coinjection of leptin and CCK enhanced the number of Fos-positive cells in the hypothalamic paraventricular nucleus by 60%, whereas leptin or CCK alone did not modify Fos expression. These results indicate the existence of a functional synergistic interaction between leptin and CCK leading to early suppression of food intake which involves CCK-A receptors and capsaicin-sensitive afferent fibers.

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Section: Discussionsupporting

confidence: 67%

mentioning

confidence: 91%

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Barrachina

Martı́nez

Wang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

405

256

View full text Add to dashboard Cite

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“…This satiation effect of leptin is synergistically enhanced by the presence of CCK (19). Extracellular single-unit recordings indicate that exogenous leptin alters the firing rate of vagal afferent fibers and that at least some of leptin-activated fibers are also activated by CCK (35). Finally, using cultured nodose ganglion neurons, we demonstrated that leptin rapidly increases cytosolic calcium in vagal afferents (18).…”

mentioning

confidence: 70%

“…Previous investigations using extracellular recording in vivo revealed that both leptin (35) and CCK (22) acutely activate Representative examples of membrane potential in cultured nodose neurons after bath application of leptin. The bars over the traces indicate the period of ligand application.…”

Section: Discussionmentioning

confidence: 99%

Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons

Peters

Ritter

Simasko

2006

American Journal of Physiology-Cell Physiology

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-We have previously reported that intraceliac infusion of leptin induces a reduction of meal size that depends on intact vagal afferents. This effect of leptin is enhanced in the presence of cholecystokinin (CCK). The mechanisms by which leptin and CCK activate vagal afferent neurons are not known. In the present study, we have begun to address this question by using patch-clamp electrophysiological techniques to examine the mechanisms by which leptin and CCK activate cultured vagal afferents from adult rat nodose ganglia. We found that leptin depolarized 41 (60%) of 68 neurons. The magnitude of membrane depolarization was dependent on leptin concentration and occurred in both capsaicin-sensitive and capsaicin-insensitive neurons. We also found that a majority (16 of 22; 73%) of nodose neurons activated by leptin were also sensitive to CCK. CCK-induced depolarization was primarily associated with the increase of an inward current (11 of 12), whereas leptin induced multiple changes in background conductances through a decrease in an outward current (7 of 13), an increase in an inward current (3 of 13), or both (3 of 13). However, further isolation of background currents by recording in solutions that contained only sodium or only potassium revealed that both leptin and CCK were capable of increasing a sodium-dependent conductance or inhibiting a potassium-dependent conductance. Our results support the hypothesis that vagal afferents are a point of convergence and integration of leptin and CCK signaling for control of food intake and suggest multiple ionic mechanisms by which leptin and CCK activate vagal afferent neurons.cholecystokinin; vagal afferents; capsaicin; satiation THE ADIPOKINE HORMONE LEPTIN and the intestinal peptide cholecystokinin (CCK) have profound effects on food intake and energy expenditure. Leptin is secreted into the systemic blood primarily by white adipose tissue (7,14). When administered exogenously, leptin induces several physiological changes, the most dramatic of which is the rapid loss of body fat (11). CCK, a peptide produced and stored within enteroendocrine I cells of the upper small intestine, is secreted in response to fat or protein in the intestinal lumen (12). When administered exogenously or released endogenously, CCK decreases meal size and evokes a behavioral pattern consistent with an enhancement of the satiation process (31). During the past 10 years, several observations (2,15,18,19) have suggested that leptin and CCK may interact synergistically at multiple levels along the neuroaxis to produce changes in food intake and energy expenditure. Indeed, recent reports from our laboratory and others suggest that such leptin-CCK synergy may even occur at the level of primary vagal afferent neurons.Vagal afferent neurons innervate a majority of the abdominal viscera and express both leptin and CCK receptors (4 -6, 17). It is well established that satiation produced by peripheral CCK involves activation of vagal afferent neurons (10,21,29,30,32). On the other hand, many effects ...

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“…Leptin is produced in the mucosa of the stomach and rapidly mobilized by feeding and high doses of exogenous cholecystokinin (Bado et al, 1998), and it appears to activate vagal afferents (Wang et al, 1997), shown to express the long form of leptin receptor (Buyse et al, 2001;Burdyga et al, 2002). Small doses of leptin infused into the celiac artery significantly decreased sucrose intake and this effect was not observed in rats with subdiaphragmatic vagotomy or perivagal capsaicin-treatment aimed to selectively ablate vagal afferent fibers.…”

Section: Stomach: Stretch Tension Leptin and Ghrelinmentioning

confidence: 99%

The vagus nerve, food intake and obesity

Berthoud

2008

Regulatory Peptides

264

199

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Food interacts with sensors all along the alimentary canal to provide the brain with information regarding its composition, energy content, and beneficial effect. Vagal afferents innervating the gastrointestinal tract, pancreas, and liver provide a rapid and discrete account of digestible food in the alimentary canal, as well as circulating and stored fuels, while vagal efferents together with the sympathetic nervous system and hormonal mechanisms codetermine the rate of nutrient absorption, partitioning, storage, and mobilization. Although vagal sensory mechanisms play a crucial role in the neural mechanism of satiation, there is little evidence suggesting a significant role in long-term energy homeostasis. However, increasing recognition of vagal involvement in the putative mechanisms making bariatric surgeries the most effective treatment for obesity should greatly stimulate future research to uncover the many details regarding the specific transduction mechanisms in the periphery and the inter-and intra-neuronal signaling cascades disseminating vagal information across the neuraxis.

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Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats

Cited by 106 publications

References 0 publications

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice

Leptin and CCK modulate complementary background conductances to depolarize cultured nodose neurons

The vagus nerve, food intake and obesity

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