Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Nogueiras, Rubén; Tovar, Sulay; Mitchell, Sharon E.; Barrett, Perry; Rayner, D V; Diéguez, Carlos; Williams, Lynda M.

doi:10.1677/joe.1.06577

Cited by 15 publications

(15 citation statements)

References 41 publications

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“…At 120 hpf, additional cells differentiate in the hypothalamus (Figures 2E and 2F, Movie S1). This pattern of expression accords with nmu expression in the adult mammalian central nervous system in hypothalamus, brainstem, and spinal cord (Austin et al, 1994; Fujii et al, 2000; Graham et al, 2003; Howard et al, 2000; Ivanov et al, 2002; Nogueiras et al, 2006; Szekeres et al, 2000). We did not observe peripheral expression of nmu in the gastrointestinal or genitourinary tracts, or in the skin, as has been reported in mammals.…”

Section: Resultssupporting

confidence: 71%

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Chiu

Rihel

Lee

et al. 2016

Neuron

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Summary Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotrophin-releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather likely acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.

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Section: Resultssupporting

confidence: 71%

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Chiu

Rihel

Lee

et al. 2016

Neuron

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“…Like other gut-brain peptides, there are sources of neuromedins intrinsic to the brain (185), possibly reflecting parallel gut/brain systems seen in other gut-brain peptides. Within the brain, most attention has been given to NMU-containing cells in hypothalamic regions important in energy balance, particularly its actions in the PVH and Arc, specifically pro-opiomelanocortin (POMC)-containing arcuate neurons (186), and also dorsomedial hypothalamus (184, 186, 187). Several non-hypothalamic regions also contain NMU-immunoreactive neurons and fibers, however, including hindbrain regions important in arousal and energy balance that are also responsive to CCK (185, 188).…”

Section: Neuromedinsmentioning

confidence: 99%

“…Moreover, commonalities in the behavioral and energetic actions of neuromedins and homologous peptides can be seen in non-mammals, even invertebrates (208-214). It has been hypothesized that one action of leptin is to stimulate the release of NMU, through which it exerts its actions on metabolism (186, 187, 203, 215). Transgenic over expression of NMU in mice leads to hypophagia and leanness (216), and deletion of the gene for NMU results in obesity, hyperphagia, and decreased physical activity (217).…”

Section: Neuromedinsmentioning

confidence: 99%

Neuropeptides Controlling Energy Balance: Orexins and Neuromedins

Nixon

Kotz

Novak

et al. 2011

Handbook of Experimental Pharmacology

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In this section we review the feeding and energy expenditure effects of orexin (also known as hypocretin) and neuromedin. Orexins are multifunctional neuropeptides that affect energy balance by participating in regulation of appetite, arousal, and spontaneous physical activity. Central orexin signaling for all functions originates in the lateral hypothalamus–perifornical area, and is likely functionally differentiated based on site of action and on interacting neural influences. The effect of orexin on feeding is likely related to arousal in some ways, but is nonetheless a separate neural process that depends on interactions with other feeding related neuropeptides. In a pattern distinct from other neuropeptides, orexin stimulates both feeding and energy expenditure. Orexin increases in energy expenditure are mainly by increasing spontaneous physical activity, and this energy expenditure effect is more potent than the effect on feeding. Global orexin manipulations, such as in transgenic models, produce energy balance changes consistent with a dominant energy expenditure effect of orexin. Neuromedins are gut-brain peptides that reduce appetite. There are gut sources of neuromedin, but likely the key appetite related neuromedin producing neurons are in hypothalamus and parallel other key anorectic neuropeptide expression in the arcuate to paraventricular hypothalamic projection. As with other hypothalamic feeding related peptides, hindbrain sites are likely also important sources and targets of neuromedin anorectic action. Neuromedin increases physical activity in addition to reducing appetite, thus producing a consistent negative energy balance effect. Together with the various other neuro-peptides, -transmitters, -modulators and –hormones, neuromedin and orexin act in the appetite network to produce changes in food intake and energy expenditure, which ultimately influences the regulation of body weight.

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“…Both NMU-R1 and NMU-R2 signal through activation of Gq/11, PLC and Ca 2+ , with the R2 subtype stimulating arachidonic acid production through activation of PLA 2 [199]. NMU is highly conserved among species, is widely distributed in the body and expressed at high levels in the brain where it mediates effects on food intake opposite to those of ghrelin [200], probably by cross-talking with the anorectic polypeptide leptin system [200, 201]. NMU also appears to play some function in the growth of neoplastic cells with expression being downregulated in cancer [202]; in fact it was demonstrated to inhibit esophageal squamous cell carcinoma cell growth [203].…”

Section: Non-type 1a Ghs Receptorsmentioning

confidence: 99%

Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors

Muccioli¹,

Baragli²,

Granata³

et al. 2007

Neuroendocrinology

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Ghrelin is a gastric polypeptide displaying strong GH-releasing activity by activation of the type 1a GH secretagogue receptor (GHS-R1a) located in the hypothalamus-pituitary axis. GHS-R1a is a G-protein-coupled receptor that, upon the binding of ghrelin or synthetic peptidyl and non-peptidyl ghrelin-mimetic agents known as GHS, preferentially couples to G_q, ultimately leading to increased intracellular calcium content. Beside the potent GH-releasing action, ghrelin and GHS influence food intake, gut motility, sleep, memory and behavior, glucose and lipid metabolism, cardiovascular performances, cell proliferation, immunological responses and reproduction. A growing body of evidence suggests that the cloned GHS-R1a alone cannot be the responsible for all these effects. The cloned GHS-R1b splice variant is apparently non-ghrelin/GHS-responsive, despite demonstration of expression in neoplastic tissues responsive to ghrelin not expressing GHS-R1a; GHS-R1a homologues sensitive to ghrelin are capable of interaction with GHS-R1b, forming heterodimeric species. Furthermore, GHS-R1a-deficient mice do not show evident abnormalities in growth and diet-induced obesity, suggesting the involvement of another receptor. Additional evidence of the existence of another receptor is that ghrelin and GHS do not always share the same biological activities and activate a variety of intracellular signalling systems besides G_q. The biological actions on the heart, adipose tissue, pancreas, cancer cells and brain shared by ghrelin and the non-acylated form of ghrelin (des-octanoyl ghrelin), which does not bind GHS-R1a, represent the best evidence for the existence of a still unknown, functionally active binding site for this family of molecules. Finally, located in the heart and blood vessels is the scavenger receptor CD36, involved in the endocytosis of the pro-atherogenic oxidized low-density lipoproteins, which is a pharmacologically and structurally distinct receptor for peptidyl GHS and not for ghrelin. This review highlights the most recently discovered features of GHS-R1a and the emerging evidence for a novel group of receptors that are not of the GHS1a type; these appear involved in the transduction of the multiple levels of information provided by GHS and ghrelin.

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Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Cited by 15 publications

References 41 publications

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Neuropeptides Controlling Energy Balance: Orexins and Neuromedins

Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors

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