Neuromedin S Is a Novel Anorexigenic Hormone

Ida, Takanori; Mori, Koichi; Miyazato, Minoru; Egi, Yutaka; Abe, Shinsuke; Nakahara, Keiko; Nishihara, Masugi; Kangawa, Kenji; Murakami, Noboru

doi:10.1210/en.2005-0107

Cited by 86 publications

(56 citation statements)

References 25 publications

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“…Icariin, a flavonol glycoside found in certain herbs, has recently been shown to stimulate NMUR2 (Zheng et al, 2005), but its mechanism of action needs to be further characterized. Recently, Neuromedin S (NMS) has been identified in rat brain and has been shown to be an endogenous ligand for NMUR1 and NMUR2 (Ida et al, 2005). In this study, intracerebroventricular injection of NMS decreased food intake in rats.…”

Section: Discussionmentioning

confidence: 70%

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

McRoberts

Berr

et al. 2006

Oncogene

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Most deaths from urinary bladder cancer are owing to metastatic disease. A reduction in Rho GDP Dissociation Inhibitor 2 (RhoGDI2) protein has been associated with increased risk of metastasis in patients with locally advanced bladder cancer, whereas in animal models, RhoGDI2 reconstitution in cells without expression results in lung metastasis suppression. Recently, we noted an inverse correlation between tumor RhoGDI2 and Neuromedin U (NMU) expression, suggesting that NMU might be a target of the lung metastasis suppressor effect of RhoGDI2. Here we evaluated whether NMU is regulated by RhoGDI2 and is functionally important in tumor progression. We used small interfering RNA knockdown of endogenous RhoGDI2 in poorly tumorigenic and nonmetastatic human bladder cancer T24 cells and observed increased NMU RNA expression. Although NMU overexpression did not increase the monolayer growth of T24 or related T24T poorly metastatic human bladder cancer cells, it did augment anchorage-independent growth for the latter. Overexpression of NMU in T24 and T24T cells significantly promoted tumor formation of both cell lines in nude mice, but did not alter the growth rate of established tumors. Furthermore, NMU-overexpressing xenografts were associated with lower animal body weight than control tumors, indicating a possible role of NMU in cancer cachexia. NMU overexpression in T24T cells significantly enhanced their lung metastatic ability. Bioluminescent in vivo imaging revealed that lung metastases in T24T grew faster than the same tumors in the subcutaneous microenvironment. In conclusion, NMU is a RhoGDI2-regulated gene that appears important for tumorigenicity, lung metastasis and cancer cachexia, and thus a promising therapeutic target in cancer.

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Section: Discussionmentioning

confidence: 70%

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

McRoberts

Berr

et al. 2006

Oncogene

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“…As far as the physiological role of NMU and NMS is concerned, experimental data suggest their involvement in the regulation of neuroendocrine axes, including the gonadotropic one (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)48,49). Our semiquantitative real-time PCR data indicate great differences in the level of expression of these neuromedins and their receptors in the endocrine glands, thereby suggesting that NMU and NMS may play different roles in the functional regulation of the endocrine system.…”

Section: Discussionmentioning

confidence: 70%

“…This neuropeptide shares with NMU the C-terminal amino-acid sequence, and was named NMS because it is highly expressed in the hypothalamic suprachiasmatic nucleus (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…NMS is a neuropeptide mainly involved in the modulation of the immune response, regulation of circadian rhythms and spermatogenesis. Moreover, NMS has been also suggested to be a potent anorexigenic hormone that acts, among others, via CRH neurons (7)(8)(9). NMU is a brain-gut peptide involved in the regulation of energy homeostasis and neuroendocrine functions (4,5,(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

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Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat

Ruciński¹,

Ziółkowska²,

Neri³

et al. 2007

Int J Mol Med

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Abstract. Neuromedin S (NMS) and neuromedin U (NMU) are regulatory peptides that share the C-terminal amino-acid sequence and act via common G protein-coupled receptors called NMUR1 and NMUR2. Semiquantitative real time-PCR showed that in the rat hypothalamus and testis NMS gene expression was markedly higher than that of the NMU gene, while the reverse occurred in the anterior pituitary and thyroid gland. Low expression of both genes was detected in the thymus, adrenal gland and ovary, whereas in the pancreatic islets only the expression of NMU mRNA was detected. In the rat hypothalamus the expression of the NMUR2 gene was strikingly higher than that of the NMUR1 gene; in contrast, in the testis and ovary the very low expression of NMUR2 contrasted with the relatively high expression of the NMUR1 gene. In the other glands examined only expression of the NMUR1 gene was found. The marked differences in the level of expression of NMU, NMS and their receptors in the hypothalamus and endocrine glands of the rat suggest that in this species such neuromedins may play different roles in the functional regulation of neuroendocrine axes.

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“…We assessed the following neuropeptides; agouti-related protein (AGRP), cocaine-and amphetamine-regulated transcript (CART), corticotropin releasing hormone (CRH), galanin (GAL), gastrin releasing peptide (GRP), melanin-concentrating hormone (MCH), neuromedin S (NMS), neuromedin U (NMU), neuropeptide B (NPB), neuropeptide S (NPS), neuropeptide W (NPW), neuropeptide Y (NPY), nucleobindin 2 (NUCB2), orexin (ORX), pituitary adenylate cyclase-activating polypeptide (PACAP), pro-opiomelanocortin (POMC), tyrotropin releasing hormone (TRH), urocortin (UCN), urocortin 2 (UCN2) and urocortin 3 (UCN3). [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] We also evaluated the hypothalamic level of NUCB2 mRNA, a candidate associated with hyperphagic feeding in TSOD mice, in another model of T2DM, db/db mice, compared with that in non-diabetic control db/+ mice.…”

mentioning

confidence: 99%

Possible Involvement of Hypothalamic Nucleobindin-2 in Hyperphagic Feeding in Tsumura Suzuki Obese Diabetes Mice

Miyata

Yamada

Kawada

2012

Biological & Pharmaceutical Bulletin

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The aim of this study was to clarify the hypothalamic neuropeptides that are associated with hyperphagic feeding in Tsumura Suzuki Obese Diabetes (TSOD) mice, a model of type 2 diabetes with polygenic abnormalities. TSOD mice showed an increase in body weight and hyperleptinemia from 1 month of age and hyperphagic feeding, hyperglycemia, hyperlipidemia and hyperinsulinemia from 3 to 12 months of age compared with age-matched non-diabetic control Tsumura Suzuki Non Obesity (TSNO) mice. The mRNA level of nucleobindin-2 (NUCB2), the precursor of the anorexigenic neuropeptide nesfatin-1, was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice from 3 to 12 months of age. The protein level of NUCB2 was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice at 3 months of age. The mRNA levels of galanin, melanin-concentrating hormone, neuropeptide Y, and pro-opiomelanocortin were significantly changed in the hypothalamus in TSOD mice at several time points. Another model of type 2 diabetes, db/db mice, which is a mutant mouse that lacks a functional leptin receptor, showed hyperphagic feeding but no change in hypothalamic NUCB2 mRNA compared with non-diabetic control db/ mice. The results suggest that the disrupted control of hypothalamic NUCB2-mediated signaling may contribute to hyperphagic feeding in TSOD mice. In addition, the mechanism for the development of hyperphagic feeding in TSOD mice is different than that in db/db mice. Key words hyperphagic feeding; nucleobindin-2; hypothalamus; obesity; diabetesThe world-wide prevalence of obesity and type 2 diabetes mellitus (T2DM) is increasing, and genetic analyses in humans are difficult since these conditions are also associated with environmental factors. Therefore, model animals are highly useful in biomedical studies and may lead to new insights into human obesity and T2DM.1) Tsumura Suzuki Obese Diabetes (TSOD) mouse has been recently established as a model animal of obese T2DM by the selective breeding of ddY mice that show both obesity and urinary glucose.2) The adiposity and significantly higher body mass index in TSOD mice compared to those in non-diabetic control Tsumura Suzuki Non Obesity (TSNO) mice are detected as early as 4 weeks of age, and are maintained until at least 18 months of age.3,4) TSOD mice showed a high level of blood glucose after the intraperitoneal injection of glucose and a blunted glucosestimulated insulin secretion compared with TSNO mice.5) In addition, the hypoglycemic response to insulin treatment in TSOD mice was blunted compared to that in TSNO mice. 5)The insulin-stimulated uptake of 2-[ 3 H] deoxyglucose and translocation of glucose transporter-4 protein were impaired in skeletal muscle and adipose tissues in TSOD mice.6,7) Thus, TSOD mice have both increased resistance to insulin and decreased insulin secretion in response to glucose. Genome-wide screening in TSOD mouse for loci linked to body weight and glucose homeostasis indicated that obesity and hyperg...

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Neuromedin S Is a Novel Anorexigenic Hormone

Cited by 86 publications

References 25 publications

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat

Possible Involvement of Hypothalamic Nucleobindin-2 in Hyperphagic Feeding in Tsumura Suzuki Obese Diabetes Mice

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