Plasticity in vagal afferent neurones during feeding and fasting: mechanisms and significance*

Dockray, Graham J.; Burdyga, Galina

doi:10.1111/j.1748-1716.2010.02219.x

Cited by 56 publications

(58 citation statements)

References 76 publications

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“…In order to further clarify the mechanism behind the observed beneficial effects in the current study, we assessed aspects of indirect calorimetry following 18 days' treatment with (pGlu-Gln)-CCK-8, [D-Leu-4]-OB3 or a combination of both peptides. Although extensive studies have been conducted on the additive effects of leptin and CCK on energy intake [4], there is much less information on their possible combined effects on locomotor activity and energy expenditure. Explorative episodes (Z-beam breaks) were elevated during the dark phase but reduced during the light phase in all mice treated with (pGlu-Gln)-CCK-8, with no overall net effect.…”

Section: Discussionmentioning

confidence: 99%

“…It is widely acknowledged that the major physiological role of CCK is in the short-term stimulation of satiety [4]. Specifically, the actions of CCK on food intake are mediated peripherally by CCK 1 receptors on vagal afferent neurons [4]. Indeed, peripherally released CCK cannot penetrate the blood-brain barrier [5].…”

Section: Introductionmentioning

confidence: 99%

“…CCK is secreted from intestinal I cells in response to fatty acids and proteins in the intestinal lumen [3]. It is widely acknowledged that the major physiological role of CCK is in the short-term stimulation of satiety [4]. Specifically, the actions of CCK on food intake are mediated peripherally by CCK 1 receptors on vagal afferent neurons [4].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

2013

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Aims/hypothesis Cholecystokinin (CCK) and leptin are important hormones with effects on energy balance. The present study assessed the biological effects of (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3, smaller isoforms of CCK and leptin, respectively. Methods The actions and overall therapeutic use of (pGluGln)-CCK-8 and [D-Leu-4]-OB3, alone and in combination, were evaluated in normal and high-fat-fed mice. Results (pGlu-Gln)-CCK-8 had prominent (p<0.01 to p< 0.001), acute feeding-suppressive effects, which were significantly augmented (p<0.05 to p<0.01) by [D-Leu-4]-OB3. In agreement, the acute dose-dependent glucose-lowering and insulinotropic actions of (pGlu-Gln)-CCK-8 were significantly enhanced by concurrent administration of [D-Leu-4]-OB3. Twice daily injection of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in high-fat-fed mice for 18 days decreased body weight (p<0.05 to p<0.001), energy intake (p<0.01), circulating triacylglycerol (p<0.01), nonfasting glucose (p<0.05 to p<0.001) and triacylglycerol deposition in liver and adipose tissue (p<0.001). All treatment regimens improved glucose tolerance (p<0.05 to p<0.001) and insulin sensitivity (p<0.001). Combined treatment with (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3 resulted in significantly lowered plasma insulin levels, normalisation of circulating LDL-cholesterol and decreased triacylglycerol deposition in muscle. These effects were superior to either treatment regimen alone. There were no changes in overall locomotor activity or respiratory exchange ratio, but treatment with (pGlu-Gln)-CCK-8 significantly reduced (p<0.001) energy expenditure. Conclusions/interpretationThese studies highlight the potential of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in the treatment of obesity and diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

2013

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“…The first site of integration of these signals occurs at the level of vagal afferent neurons (VAN), which project to and stimulate second-order neurons in the dorsal vagal complex of the hindbrain (27). VAN express receptors for many of the anorexigenic and orexigenic hormones released from the gut wall and mediate changes in gastrointestinal function and food intake in response to luminal nutrients (18).…”

mentioning

confidence: 99%

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

152

142

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de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 301: E187-E195, 2011. First published April 26, 2011; doi:10.1152/ajpendo.00056.2011.-Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.lipopolysaccharide; high-fat diet; suppressor of cytokine signaling-3 THE GUT PLAYS A CRUCIAL ROLE in sensing luminal contents that is important for the efficient digestion and absorption of ingested nutrients but also in integration of other physiological processes that regulate metabolism and energy expenditure, such as pancreatic ␤-cell function, hepatic function, and also food intake (34). In response to the presence or absence of food, enteroendocrine cells of the gut release anorexic or orexigenic hormones, respectively. The first site of integration of these signals occurs at the level of vagal afferent neurons (VAN), which project to and stimulate second-order neurons in the dorsal vagal complex of the hindbrain (27). VAN express receptors for many of the anorexigenic and orexigenic hormones released from the gut wall and mediate changes in gastrointestinal function and food intake in response to luminal nutrients (18).Leptin is a gut and adipose tissue-derived hormone that regulates a range of biological functions and processes, including energy intake and expenditure, body fat, neuroendocrine systems...

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“…In the present study, it was demonstrated that the ablation of ARP neurons markedly induced Egr1 expression in the majority of known targets of POMC and ARP neurons, indicating that the loss of ARP neurons leads to disinhibition of postsynaptic neurons, which eventually results in anorexia. Egr1 has been observed to stimulate CART expression in certain types of neurons (17,23). CART peptides are widely distributed in the CNS and are known to suppress food intake (24,25) and stimulate Fos expression in a number of brain areas when administered centrally (26,27).…”

Section: Disscussionmentioning

confidence: 99%

Functional profiling of immediate early gene Egr1 in an anorexic mouse model

Huang

Jiang

Yuan

2013

Molecular Medicine Reports

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Abstract.A small population of neurons in the hypothalamus is known to promote food intake by releasing inhibitory agouti-related peptide (ARP) and neuropeptide Y to broad postsynaptic areas. Acute ablation of ARP neurons in adult mice leads to rapid loss of appetite and the development of an anorexic phenotype. Recent studies have suggested that ablation of ARP neurons removes critical inhibition of postsynaptic neurons, resulting in hyperexcitation of selected downstream neurons. Left uncontrolled, this neuronal hyperactivation is hypothesized to induce starvation. However, the cellular mechanism underlying the control of excitability of postsynaptic neurons in response to the ablation of ARP neurons is poorly understood. The present study aimed to determine the functional correlation between ARP neurons and an immediate early gene, early growth response factor-1 (Egr1), in postsynaptic neurons in the context of energy homeostasis. Egr1 expression levels were analyzed in different postsynaptic areas upon acute ablation of ARP neurons. As ARP neurons increase appetite by inhibiting the pro-opiomelanocortin pathway, it was also investigated whether blockade of melanocortin signaling affects Egr1 expression in ARP neuron-ablated mice. The results suggested that ablation of ARP neurons induced robust expression of Egr1 in numerous common postsynaptic targets of ARP and pro-opiomelanocortin neurons. When ARP neurons were acutely ablated, it was demonstrated that Egr1 induction was attenuated by chronic blockade of the melanocortin signaling pathway in the arcuate nucleus, but not in other downstream regions. Further analysis of the Egr1 signaling cascade may aid in differentiating the functional involvement of postsynaptic targets of ARP neurons in the control of energy metabolism.

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Plasticity in vagal afferent neurones during feeding and fasting: mechanisms and significance*

Cited by 56 publications

References 76 publications

Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Functional profiling of immediate early gene Egr1 in an anorexic mouse model

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