Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

Martínez, Vanesa G.; O’Driscoll, Lorraine

doi:10.1373/clinchem.2014.231753

Cited by 102 publications

(109 citation statements)

References 132 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Many functions have been described for NMU (1). Its impact on energy homeostasis, including food intake and glucose metabolism, has been largely described, although underlying mechanisms are still up for discussion.…”

Section: Discussionmentioning

confidence: 99%

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal‐dependent mechanisms

et al. 2019

View full text Add to dashboard Cite

The gut‐brain peptide neuromedin U (NMU) decreases food intake and body weight and improves glucose tolerance. Here, we characterized NMU as an enteropeptide and determined how it impacts glucose excursion. NMU was expressed predominantly in the proximal small intestine, and its secretion was triggered by ingestion of a mixed meal. Although a single peripheral injection of NMU in C57BL/6NRj mice prevented the rise of glycemia upon an oral but not an intraperitoneal load of glucose, it unexpectedly prevented insulin secretion, only slightly improved peripheral insulin sensitivity, and barely reduced intestinal glucose absorption. Interestingly, peripheral administration of NMU abrogated gastric emptying. NMU receptors 1 and 2 were detected in pyloric muscles and NMU was able to directly induce pyloric contraction in a dose‐dependent manner ex vivo in isometric chambers. Using a modified glucose tolerance test, we demonstrate that improvement of oral glucose tolerance by NMU was essentially, if not exclusively, because of its impact on gastric emptying. Part of this effect was abolished in vagotomized (VagoX) mice, suggesting implication of the vagus tone. Accordingly, peripheral injection of NMU was associated with increased number of c‐FOS–positive neurons in the nucleus of the solitary tract, which was partly prevented in VagoX mice. Finally, NMU kept its ability to improve oral glucose tolerance in obese and diabetic murine models. Together, these data demonstrate that NMU is an enteropeptide that prevents gastric emptying directly by triggering pylorus contraction and indirectly through vagal afferent neurons. This blockade consequently reduces intestinal nutrient absorption and thereby results in an apparent improved tolerance to oral glucose challenge.—Jarry, A.‐C., Merah, N., Cisse, F., Cayetanot, F., Fiamma, M.‐N., Willemetz, A., Gueddouri, D., Barka, B., Valet, P., Guilmeau, S., Bado, A., Le Beyec, J., Bodineau, L., Le Gall, M. Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal‐dependent mechanisms. FASEB J. 33, 5377–5388 (2019). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 99%

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal‐dependent mechanisms

et al. 2019

View full text Add to dashboard Cite

show abstract

“…ab16045; Abcam), anti-GAPDH (PA1-987; Pierce Protein Biology, Thermo Scientific), or β-actin (no. sc-47778; Santa Cruz Biotechnology); although NmU and NmS antibodies detect the corresponding propeptides [7], expression patterns were corroborated throughout the study by nearly identical mRNA profiles. Membranes were then washed with PBS containing 0.1% Tween 20 (Sigma-Aldrich) and incubated for 1 h with their respective secondary antibodies conjugated to horseradish peroxidase (HRP; Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…Neuromedin U (NmU; U for uterus) was named for its ability to induce contractions on ex vivo uterine strips; yet, there is a growing list of functions associated with NmU that includes regulation of appetite, diminution of insulin secretion, release of different hormones, and smooth muscle contraction (of various organs: blood vessels, gut, and uterus) [7, 8]. NmU exerts its actions by binding to two G protein-coupled receptors: neuromedin U receptor 1 (NmU-R1; FM-3 or GPR66) and NmU-R2 (FM-4) [8–12].…”

Section: Introductionmentioning

confidence: 99%

Uterotonic Neuromedin U Receptor 2 and Its Ligands Are Upregulated by Inflammation in Mice and Humans, and Elicit Preterm Birth

Nadeau-Vallée

Boudreault

Leimert

et al. 2016

Biology of Reproduction

View full text Add to dashboard Cite

Uterine labor requires the conversion of a quiescent (propregnancy) uterus into an activated (prolabor) uterus, with increased sensitivity to endogenous uterotonic molecules. This activation is induced by stressors, particularly inflammation in term and preterm labor. Neuromedin U (NmU) is a neuropeptide known for its uterocontractile effects in rodents. The objective of the study was to assess the expression and function of neuromedin U receptor 2 (NmU-R2) and its ligands NmU and the more potent neuromedin S (NmS) in gestational tissues, and the possible implication of inflammatory stressors in triggering this system. Our data show that NmU and NmS are uterotonic ex vivo in murine tissue, and they dose-dependently trigger labor by acting specifically via NmU-R2. Expression of NmU-R2, NmU, and NmS is detected in murine and human gestational tissues by immunoblot, and the expression of NmS in placenta and of NmU-R2 in uterus increases considerably with gestation age and labor, which is associated with amplified NmU-induced uterocontractile response in mice. NmU- and NmS-induced contraction is associated with increased NmU-R2-coupled Ca++ transients, and Akt and Erk activation in murine primary myometrial smooth muscle cells (mSMCs), which are potentiated with gestational age. NmU-R2 is upregulated in vitro in mSMCs and in vivo in uterus in response to proinflammatory interleukin 1beta (IL1beta), which is associated with increased NmU-induced uterocontractile response and Ca++ transients in murine and human mSMCs; additionally, placental NmS is markedly upregulated in vivo in response to IL1beta. In human placenta at term, immunohistological analysis revealed NmS expression primarily in cytotrophoblasts; furthermore, stimulation with lipopolysaccharide (LPS; Gram-negative endotoxin) markedly upregulates NmS expression in primary human cytotrophoblasts isolated from term placentas. Correspondingly, decidua of women with clinical signs of infection who delivered preterm display significantly higher expression of NmS compared with those without infection. Importantly, in vivo knockdown of NmU-R2 prevents LPS-triggered preterm birth in mice and the associated neonatal mortality. Altogether, our data suggest a critical role for NmU-R2 and its ligands NmU and NmS in preterm labor triggered by infection. We hereby identify NmU-R2 as a relevant target for preterm birth.

show abstract

“…In addition to VIP, recent studies have identified cholinergic neurons as potent activators of intestinal and lung ILC2s, acting via production of the neuropeptide neuromedin U (NMU). The sequence of NMU is highly conserved between species, suggesting that it is an ancient molecule playing an important role that has been preserved throughout evolution . NMU is widely distributed throughout the body; its highest concentrations are found within the gastrointestinal tract and it is usually detected in the ENS .…”

Section: Nervous System‐ilc Interactions In the Maintenance Of Barriementioning

confidence: 99%

“…The sequence of NMU is highly conserved between species, suggesting that it is an ancient molecule playing an important role that has been preserved throughout evolution . NMU is widely distributed throughout the body; its highest concentrations are found within the gastrointestinal tract and it is usually detected in the ENS . Moreover, Nmu expression has been detected in sensory neurons innervating the lung with cell bodies residing in the DRG, but not in the nodose/jugular ganglia .…”

Section: Nervous System‐ilc Interactions In the Maintenance Of Barriementioning

confidence: 99%

Neuroendocrine regulation of innate lymphoid cells

Quatrini

Vivier

Ugolini

2018

Immunological Reviews

View full text Add to dashboard Cite

SummaryThe activities of the immune system in repairing tissue injury and combating pathogens were long thought to be independent of the nervous system. However, a major regulatory role of immunomodulatory molecules released locally or systemically by the neuroendocrine system has recently emerged. A number of observations and discoveries support indeed the notion of the nervous system as an immunoregulatory system involved in immune responses. Innate lymphoid cells (ILCs), including natural killer (NK) cells and tissue‐resident ILCs, form a family of effector cells present in organs and mucosal barriers. ILCs are involved in the maintenance of tissue integrity and homeostasis. They can also secrete effector cytokines rapidly, and this ability enables them to play early roles in the immune response. ILCs are activated by multiple pathways including epithelial and myeloid cell‐derived cytokines. Their functions are also regulated by mediators produced by the nervous system. In particular, the peripheral nervous system, through neurotransmitters and neuropeptides, works in parallel with the hypothalamic‐pituitary‐adrenal and gonadal axis to modulate inflammatory events and maintain homeostasis. We summarize here recent findings concerning the regulation of ILC activities by neuroendocrine mediators in homeostatic and inflammatory conditions.

show abstract

Neuromedin U: A Multifunctional Neuropeptide with Pleiotropic Roles

Cited by 102 publications

References 132 publications

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal‐dependent mechanisms

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal‐dependent mechanisms

Uterotonic Neuromedin U Receptor 2 and Its Ligands Are Upregulated by Inflammation in Mice and Humans, and Elicit Preterm Birth

Neuroendocrine regulation of innate lymphoid cells

Contact Info

Product

Resources

About