Nesfatin‐1 Influences the Excitability of Paraventricular Nucleus Neurones

Price, Christopher J.; Hoyda, Ted D.; Samson, Willis K.; Ferguson, Alastair V.

doi:10.1111/j.1365-2826.2007.01641.x

Cited by 76 publications

(54 citation statements)

References 15 publications

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“…Similarly to our findings in previous studies we performed in the paraventricular (PVN) and arcuate (ARC) nuclei of the hypothalamus (19,20), nesfatin-1 exerted depolarizing or hyperpolarizing effects on different subsets of mNTS neurons tested. These opposing actions of the same peptide can potentially be attributed to the fact that nesfatin-1 may be affecting functionally separate populations of neurons that ultimately exert differential effects on cardiovascular regulation and energy homeostasis.…”

Section: Discussionsupporting

confidence: 67%

“…Furthermore, central or peripheral injections of nesfatin-1 result in c-Fos expression in NTS neurons (16,22). However, despite the detailed knowledge of the central expression of nesfatin-1, to date there is minimal data describing the specific functional roles of nesfatin-1 in these autonomic nuclei, and what information is available has centered only on actions in the hypothalamus (16,19,20,28,29). The present study was thus undertaken to explore the cellular correlates and functional roles of nesfatin-1 actions in the medullary NTS using current-clamp electrophysiology, post hoc single cell reverse transcriptase polymerase reaction (RT-PCR), and microinjection techniques.…”

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confidence: 99%

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Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Mimee

Smith

Ferguson

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Nesfatin-1 has been identified as one of the most potent centrally acting anorexigenic peptides, and it has also been shown to play important roles in the control of cardiovascular function. In situ hybridization and immunohistochemical studies have revealed the expression of nesfatin-1 throughout the brain and, in particular, in the medullary autonomic gateway known as the nucleus of the solitary tract (NTS). The present study was thus undertaken to explore the cellular correlates and functional roles of nesfatin-1 actions in the medial NTS (mNTS). Using current-clamp electrophysiology recordings from mNTS neurons in slice preparation, we show that bathapplied nesfatin-1 directly influences the excitability of the majority of mNTS neurons by eliciting either depolarizing (42%, mean: 7.8 Ϯ 0.8 mV) or hyperpolarizing (21%, mean: Ϫ8. 2 Ϯ 1.0 mV) responses. These responses were observed in all electrophysiologically defined cell types in the NTS and were site specific and concentration dependent. Furthermore, post hoc single cell reverse transcriptase polymerase reaction revealed a depolarizing action of nesfatin-1 on NPY and nucleobindin-2-expressing mNTS neurons. We have also correlated these actions of nesfatin-1 on neuronal membrane potential with physiological outcomes, using in vivo microinjection techniques to demonstrate that nesfatin-1 microinjected into the mNTS induces significant increases in both blood pressure (mean AUC ϭ 3354.1 Ϯ 750.7 mmHg·s, n ϭ 6) and heart rate (mean AUC ϭ 164.8 Ϯ 78.5 beats, n ϭ 6) in rats. Our results provide critical insight into the circuitry and physiology involved in the profound effects of nesfatin-1 and highlight the NTS as a key structure mediating these autonomic actions. microinjection; platch clamp; peptides NESFATIN-1 has been identified as one of the most potent centrally acting anorexigenic peptides (17). An 82 amino acid cleavage product of the nucleobindin-2 (NUCB2) protein, nesfatin-1 acutely and chronically reduces feeding in rodents when injected either intracerebroventricularly or peripherally, and these effects are dependent on melanocortin and oxytocin signaling (16,17,22,29). Furthermore, treatment with nesfatin-1 neutralizing antibodies markedly increases food consumption and weight gain in animals, underscoring the critical physiological, tonic inhibitory control this peptide exerts over ingestive behaviors (17). In addition to its remarkable effects on food intake, nesfatin-1 has also been shown to play important roles in the control of cardiovascular function, water intake, blood glucose regulation, stress responses, and puberty onset (6,8,23,28).In line with its numerous functions, comprehensive immunohistochemical studies have revealed a widespread distribution of nesfatin-1 throughout the brain. Notably, the nesfatin-1 peptide is strongly expressed in regions involved in the control of energy homeostasis and autonomic function in both hypothalamic and medullary centres (5), including the autonomic gateway known as the nucleus of the solitary tract (...

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Section: Discussionsupporting

confidence: 67%

mentioning

confidence: 99%

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Mimee

Smith

Ferguson

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…A study reported that nesfatin-1 has either hyperpolarizing or depolarizing effects on most neurons in the PVN (39). In addition, glucose and insulin may directly activate nesfatin-1 neurons in PVN (40).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Nesfatin-1/NUCB2 Knockdown Augments Hepatic Gluconeogenesis That Is Correlated With Inhibition of mTOR-STAT3 Signaling Pathway in Rats

Yang

Chen

et al. 2014

Diabetes

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Nesfatin-1, an 82-amino acid neuropeptide, has recently been characterized as a potent metabolic regulator. However, the metabolic mechanisms and signaling steps directly associated with the action of nesfatin-1 have not been well delineated. We established a loss-of-function model of hypothalamic nesfatin-1/NUCB2 signaling in rats through an adenoviral-mediated RNA interference. With this model, we found that inhibition of central nesfatin-1/NUCB2 activity markedly increased food intake and hepatic glucose flux and decreased glucose uptake in peripheral tissue in rats fed either a normal chow diet (NCD) or a highfat diet (HFD). The change of hepatic glucose fluxes in the hypothalamic nesfatin-1/NUCB2 knockdown rats was accompanied by increased hepatic levels of glucose-6-phosphatase and PEPCK and decreased insulin receptor, insulin receptor substrate 1, and AKT kinase phosphorylation. Furthermore, knockdown of hypothalamic nesfatin-1 led to decreased phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) and the subsequent suppressor of cytokine signaling 3 levels. These results demonstrate that hypothalamic nesfatin-1/NUCB2 plays an important role in glucose homeostasis and hepatic insulin sensitivity, which is, at least in part, associated with the activation of the mTOR-STAT3 signaling pathway. Diabetes 2014;63:123463: -124763: | DOI: 10.2337 The hypothalamus, where numerous neuropeptides and transmitters are released to control essential body functions, has been considered a key integrator in the central control of food intake and energy balance (1,2). Oh-I et al. (3) discovered nesfatin-1, an 82-amino acid polypeptide, while searching for new appetite-controlling signals. Nesfatin-1 is the cleavage product of the calcium and DNA-binding protein nucleobindin2 (NUCB2),

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“…Nesfatin/ NuCB2 expression is modulated by starvation and refeeding in the PVN and SON [3,10]. Nesfatin-1 influences the excitability of a large proportion of different subpopulations of neurons located in the PVN [11]. Nesfatin-1 neurons in the PVN and SON co-expressed oxytocin and vasopressin [10].…”

Section: Peripheral Nesfatin/nucb2 Expressionmentioning

confidence: 99%

Nesfatin-1: An Overview and Future Clinical Application

et al. 2009

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Abstract. Nesfatin/nucleobindin 2 (NuCB2) is expressed in the appetite-control hypothalamic nuclei and brainstem nuclei. Nesfatin/NuCB2 expression in the paraventricular nucleus of the hypothalamus was modulated by starvation and refeeding. intracerebroventricular administration of nesfatin-1 dose-dependently inhibited food intake for 6 hours in male Wistar and leptin resistant, zucker fatty rats. intraperitoneal administration of nesfatin-1 and its mid-segment (m30) dosedependently inhibited food intake for 3 hours in male iCr mice. intraperitoneal administration of m30 also decreased food intake in leptin-resistant, genetically obese (ob/ob), diabetic (db/db) mice and mice fed a 45% high fat diet for 28 days. intraperitoneal administration of m30 increased proopiomelanocortin and cocaine-and amphetamine-related peptide mRNA expression in the nucleus of the solitary tract of mice. In addition, intranasal administration of nesfatin-1 significantly inhibited food intake for 6 hours in male Wistar rats. We summarize recent observations about nesfatin-1, and attempt to present future direction of nesfatin-1 research for developing a new anti-obesity treatment.Key words: Nesfatin-1, Leptin, Food intake, Body weight, Obesity (Endocrine Journal 56: [537][538][539][540][541][542][543] 2009) We have proposed the concept of brain-adipose axis that endogenous molecule, expressed in both hypothalamus and adipose tissue, exists in the general circulation, and is involved in the regulation of both feeding behavior, and the determination of size and/ or number of adipocytes [1]. Troglitazone, peroxisome proliferator-activated receptor-γ (PPARγ) agonist, might modify the satiety in type 2 diabetic patients [2], and we attempted to identify a new protein regulated by PPARγ, which modulates feeding behavior. By using a subtraction-cloning assay, we found a new anorexigenic protein increased by troglitazone, and named it NEFa/nucleobindin 2 encoded satietyand fat-influencing protein (nesfatin), corresponding to NEFa/nucleobindin 2 (NuCB2), which had been reported to be a secreted protein of unknown function [3]. Nesfatin/NuCB2 is composed of a signal peptide of 24 amino acids and a protein structure containing 396 amino acids (Fig. 1). The homology of the amino acid sequence of nesfatin/NuCB2 is highly conserved in humans, mice and rats. in this review, we summarize recent observation about the physiological role of nesfatin-1, and discuss future direction for the research of this anorexigenic protein. Anorexigenic effect of nesfatin and its fragmentsNesfatin/NuCB2 is expressed in the appetite-control hypothalamic nuclei such as paraventricular nucleus (PVN), arcuate nucleus (ARC), supraoptic nucleus (SON) of hypothalamus, lateral hypothalamic area (LHa), and zona incerta in rats [3]. Nesfatin-1-immunoreactivity was also found in the brainstem nuclei such as nucleus of the solitary tract (NTS) and dorsal nucleus of vagus [3,4]. Selective reduction of nesfatin/NUCB2 mRNA expression in the PVN of rat was found under starved cond...

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Nesfatin‐1 Influences the Excitability of Paraventricular Nucleus Neurones

Cited by 76 publications

References 15 publications

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function

Hypothalamic Nesfatin-1/NUCB2 Knockdown Augments Hepatic Gluconeogenesis That Is Correlated With Inhibition of mTOR-STAT3 Signaling Pathway in Rats

Nesfatin-1: An Overview and Future Clinical Application

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