Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats

Nakahara, Keiko; Katayama, Tetsuro; Maruyama, Kouichi; Ida, Takanori; Mori, Koichi; Miyazato, Minoru; Kangawa, Kenji; Murakami, Noboru

doi:10.1677/joe-10-0081

Cited by 22 publications

(13 citation statements)

References 44 publications

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“…administration of NmU to rats induced stress-related behavior (37,(63)(64)(65)(66). This was coupled to an increase in c-Fos expression, increased depolarization, and neuronal firing by cells of the PVN following NmU administration (67)(68)(69)(70)(71). Moreover, significant increases in plasma concentrations of stressrelated hormones (ACTH, corticosterone, adrenalin) were also detected following central or subcutaneous administration of NmU; these results are in agreement with low ACTH plasma concentrations detected in NmU Ϫ/Ϫ mice (57,65,69,(72)(73)(74)(75).…”

Section: Stress Responsesupporting

confidence: 81%

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

2015

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BACKGROUND Neuromedin U (NmU) belongs to the neuromedin family, comprising a series of neuropeptides involved in the gut–brain axis and including neuromedins B and C (bombesin-like), K (neurokinin B), L (neurokinin A or neurotensin), N, S, and U. CONTENT Although initially isolated from porcine spinal cord on the basis of their ability to induce uterine smooth muscle contraction, these peptides have now been found to be expressed in several different tissues and have been ascribed numerous functions, from appetite regulation and energy balance control to muscle contraction and tumor progression. NmU has been detected in several species to date, particularly in mammals (pig, rat, rabbit, dog, guinea pig, human), but also in amphibian, avian, and fish species. The NmU sequence is highly conserved across different species, indicating that this peptide is ancient and plays an important biological role. Here, we summarize the main structural and functional characteristics of NmU and describe its many roles, highlighting the jack-of-all-trades nature of this neuropeptide. SUMMARY NmU involvement in key processes has outlined the possibility that this neuropeptide could be a novel target for the treatment of obesity and cancer, among other disorders. Although the potential for NmU as a therapeutic target is obvious, the multiple functions of this molecule should be taken into account when designing an approach to targeting NmU and/or its receptors.

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Section: Stress Responsesupporting

confidence: 81%

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

2015

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“…Administration of NMU could not suppress food intake or increase oxygen consumption and body temperature in CRH-knockout mice (Hanada et al 2003). Administration of NMS could upregulate the CRH mRNA levels in the brain, and the NMS-mediated inhibition of food intake could be attenuated by pretreatment with the antagonist of CRH , Nakahara et al 2010. In goldfish, a significant increase in the expression of crh mRNA was observed after injection with Nmu-21 peptide, and the anorexigenic effect of this peptide was erased by treatment with the antagonist of Crh receptor (Maruyama et al 2008).…”

Section: Discussionmentioning

confidence: 94%

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper

Xiao

Liu

et al. 2015

Journal of Molecular Endocrinology

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Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orangespotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu-and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhb) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshb), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper.

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“…The effects of NMU signaling on total food consumption have been previously examined (5–14,18, 21, 35, 36). It has been shown that intra-PVN and ICV NMU regulate intake of a standard diet in rodents and that NMUR2 mediates preference for high-fat food (9).…”

Section: Resultsmentioning

confidence: 99%

“…However, further understanding of the regions and pathways involved is essential to interpreting the behavioral effects of NMU. While the effects of NMU on food intake and body weight have been evaluated (8, 11, 18–21), little consideration has been given to the reinforcing properties of food. However, NMU has recently been shown to regulate the reinforcement value of alcohol (22), and signaling between NMU and its CNS receptor, NMUR2, regulates preference for obesogenic food (9).…”

Section: Introductionmentioning

confidence: 99%

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus

2016

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BACKGROUNDMotivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be Neuromedin U (NMU), a highly-conserved neuropeptide which influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects.METHODSThe motivational state for a particular reinforcer (e.g., high-fat food) can be assessed using a progressive ratio schedule of reinforcement under which an increasing number of lever presses are required to obtain subsequent reinforcers. Here, we have employed a progressive ratio operant responding paradigm in combination with an assessment of cumulative food intake to evaluate the effects of NMU administration in rats, and identify the brain regions mediating these effects.RESULTSWe found that peripheral administration of NMU decreases operant responding for high-fat food in rats. Evaluation of Fos-like immunoreactivity in response to peripheral NMU indicated the PVN and dorsal raphe nucleus (DRN) as sites of action for NMU. NMU infusion into either region mimics the effects of peripheral NMU on food intake and operant responding for food. NMU-containing projections from the lateral hypothalamus (LH) to the PVN and DRN were identified as an endogenous source of NMU.CONCLUSIONSThese results identify the DRN as a site of action for NMU, demonstrate that the LH provides endogenous NMU to the PVN and DRN, and implicate NMU signaling in the PVN and DRN as a novel regulator of motivation for high-fat foods.

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Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats

Cited by 22 publications

References 44 publications

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus

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