Disease relevance of Nmu

• In contrast to the NMU peptide-deficient mice, NMUR2 KO mice appeared normal with regard to stress, anxiety, body weight regulation, and food consumption [1].
• NMU-deficient mice were resistant against cecal ligation puncture- as well as LPS-induced septic shock [2].
• Here we show that mice lacking the gene encoding NMU (Nmu(-/-) mice) develop obesity [3].
• Obese Nmu(-/-) mice developed hyperleptinemia, hyperinsulinemia, late-onset hyperglycemia and hyperlipidemia [3].
• Nmu(-/-) mice showed increased body weight and adiposity, hyperphagia, and decreased locomotor activity and energy expenditure [3].

Psychiatry related information on Nmu

• These results indicate that NMU plays an important role in the regulation of feeding behavior and energy metabolism independent of the leptin signaling pathway [3].
• There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding [4].

High impact information on Nmu

• Notably, however, treatment with exogenous leptin was effective in reducing body weight in obese Nmu(-/-) mice [3].
• In addition, central leptin administration did not affect NMU gene expression in the hypothalamus of rats [3].
• These data indicate that NMU promotes mast cell-mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell-mediated inflammatory diseases [5].
• The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells [5].
• NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca(2+) mobilization and degranulation in peritoneal mast cells [5].

Biological context of Nmu

• We show that behavioral effects, such as suppression of food intake, enhanced pain response, and excessive grooming induced by intracerebroventricular NMU administration were abolished in the NMUR2 knockout (KO) mice, establishing a causal role for NMUR2 in mediating NMU's central effects on these behaviors [1].
• Furthermore, facilitated excitatory synaptic transmission in spinal dorsal horn neurons, a mechanism by which NMU stimulates pain, did not occur in NMUR2 KO mice [1].
• Neuromedin U (NMU) is a neuropeptide involved in appetite, circadian rhythm, and pronociception [2].
• Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F(1)-W/W(v) mice [5].
• In a mouse Th2 cell line (D10.G4.1), a single class of high affinity saturable binding sites for (125)I-labeled NmU (K(D) 364 pM and B(max) 1114 fmol/mg protein) was identified, and mRNA encoding NmU-1R, but not NmU-2R, was present [6].

Anatomical context of Nmu

• Species-dependent smooth muscle contraction to Neuromedin U and determination of the receptor subtypes mediating contraction using NMU1 receptor knockout mice [7].
• This investigation uncovered a number of previously unidentified NMU-mediated responses: contraction of rat lower esophageal sphinster (LES), rat ileum, mouse gallbladder, enhancement of electrically evoked contractions in rat and mouse vas deferens, and a considerable degree of cross-species differences [7].
• The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock [2].
• Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell-deficient WBB6F(1)-W/W(v) mice, did not occur in NMU-deficient mice [5].
• Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system [5].

Associations of Nmu with chemical compounds

• These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide [4].
• The plasma levels of insulin, leptin, total cholesterol, triglycerides and free fatty acids were higher in the Nmu(-/-) than wild-type mice [8].
• In an attempt to identify a synthetic NmU peptide that would exhibit selectivity at one of the two receptors, we examined the functional activity of eight alanine-substituted NmU-8 peptides [9].

Regulatory relationships of Nmu

• However, the NMU receptor NMU-R1 has been shown to be expressed in immune cells and NMU promotes mast cell-dependent inflammation [2].

Other interactions of Nmu

• In this study, we demonstrated that NMU plays an important role in IL-6 production in macrophages [2].
• IL-6 but not TNF-alpha levels were markedly reduced in LPS-treated NMU-deficient mice compared with wild type mice [2].
• A range of isolated organ in vitro bioassays were carried out, which were chosen to re-confirm previous literature reports (uterine and stomach fundus contraction) and also to explore potentially novel smooth muscle responses to NMU [7].

Analytical, diagnostic and therapeutic context of Nmu

• These results provide significant insights into a functional dissection of the differential contribution of peripherally or centrally acting NMU system [1].
• In situ hybridization studies revealed that NMU is expressed in several regions of the mouse hypothalamus associated with the regulation of energy balance [10].
• Furthermore, NMU-overexpressing xenografts were associated with lower animal body weight than control tumors, indicating a possible role of NMU in cancer cachexia [11].
• Systemic perfusion of NMU (rat, NMU-23) dose-dependently (0.2, 0.5, 1, and 2.5 microM) potentiated both the background activity and noxious pinch-evoked response of nociceptive or wide dynamic range, but not non-nociceptive, dorsal horn neurons [12].

References