The gut–brain peptide neuromedin U is involved in the mammalian circadian oscillator system

Nakahara, Keiko; Hanada, Reiko; Murakami, Noboru; Teranishi, Hitoshi; Ohgusu, Hideko; Fukushima, Nobuhiro; Moriyama, Maiko; Ida, Takanori; Kangawa, Kenji; Kojima, Masayasu

doi:10.1016/j.bbrc.2004.04.014

Cited by 73 publications

(63 citation statements)

References 43 publications

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“…Although the mechanism(s) responsible for this shift in substrate oxidation are not known, it is possible that NmU overexpression provoked subtle changes in circadian oscillations during food deprivation and refeeding. Supporting this hypothesis are studies in rats and mice showing that NmU is expressed in the SCN (Howard et al 2000, Nakahara et al 2004, and that i.c.v. injections of NmU to rats during the subjective light phase induces a phase shift in the circadian rhythm (Nakahara et al 2004).…”

Section: Discussionmentioning

confidence: 88%

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice

Kowalski¹,

Spar²,

Markowitz³

et al. 2005

Journal of Endocrinology

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Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O 2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.

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Section: Discussionmentioning

confidence: 88%

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice

Kowalski¹,

Spar²,

Markowitz³

et al. 2005

Journal of Endocrinology

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“…Alternatively, NMU may act on an undefined receptor other than these two. Several studies have demonstrated, on the other hand, that the mRNAs encoding NMU, NMS, NMU1R, and NMU2R each have an intrinsic rhythmic expression in the SCN or hypothalamus with a different circadian pattern (Graham et al 2003, Nakahara et al 2004a,b, Mori et al 2005, Jethwa et al 2006. As the SCN sends neural projections into the PVN and Arc (Vrang et al 1995, Saeb-Parsy et al 2000, these different rhythmic expressions may be related to the different effects of NMS and NMU.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence accumulated over the last decade has suggested that NMU and/or NMS are involved in the central regulation of feeding, energy homeostasis, stress, and circadian rhythms, probably through NMUR2 , Hanada et al 2001, Ivanov et al 2002, Nakahara et al 2004a,b, Ida et al 2005, Novak et al 2006, Zeng et al 2006, Novak 2009, Peier et al 2009). I.c.v.…”

Section: Introductionmentioning

confidence: 99%

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

Nakahara

Katayama

Maruyama³

et al. 2010

Journal of Endocrinology

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We compared the central mechanisms of feeding suppression by the anorexigenic hormones neuromedin U (NMU) and neuromedin S (NMS) in rats. I.c.v. injection of either NMU or NMS dose dependently decreased 3-h food intake during the first quarter of a dark period. Pretreatment involving i.c.v. injection of a specific anti-NMS IgG blocked the suppression of food intake induced by i.c.v.-and i.p.-injected leptin, but anti-NMU IgG elicited no blockade. Quantitative PCR analysis revealed that i.c.v. injection of NMU or NMS caused a dose-dependent increase in CRH and proopiomelanocortin mRNA expression in the paraventricular nucleus (PVN) and arcuate nucleus (Arc) respectively. In tissue cultures of the Arc, secretion of a-melanocyte-stimulating hormone was stimulated by NMU and NMS, with more potent stimulation by NMS. The time-course curves of the increase in neuronal firing rate in Arc slices in response to NMU and NMS showed almost the same pattern, with a peak 10-15 min after treatment, whereas the time-course curves for the PVN slices differed between NMU and NMS. These results suggest that NMS and NMU may share anorexigenic effects, depending on physiological conditions.

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“…NMU neurons are present in hindbrain and hypothalamic nuclei that sense energy balance signals [19,34,35,84], and alteration of NMU release in the PVN may be one mechanism through which these brain regions regulate energy balance. In addition, another hypothalamic region contains neuromedin-expressing neurons, namely the suprachiasmatic nucleus (SCN), the primary circadian clock in mammals [67,68]. Because the SCN projects to the parovcellar region of the PVN [28,47], the SCN may impose a daily rhythm on physical activity and energy expenditure in part though the actions of neuromedin in the PVN.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity

2007

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Obesity is associated with a decrease in energy expenditure relative to energy intake. The decrease in physical activity associated with obesity in several species, including humans, contributes to decreased energy expenditure. Several hormones and neuropeptides that affect appetite also modulate physical activity, including neuromedin U (NMU), a peptide found in the gut and brain. We have demonstrated that NMU microinjected into the hypothalamic paraventricular nucleus (PVN) in rats increases the energy expenditure associated with physical activity, called non-exercise activity thermogenesis (NEAT). Here we examined whether obesity in rats is related to decreased sensitivity of the PVN to the locomotor-activating effect of NMU. Diet-induced obese (DIO) rats and lean, dietresistant (DR) rats were given PVN microinjections of increasing doses of NMU both before and after one month on a high-fat diet. We found that NMU increases physical activity, energy expenditure, and NEAT in a dose-dependent manner in both DR and DIO rats, both before and after one month on the high-fat diet. Before high-fat feeding, the obesity-prone and lean rats showed similar levels of physical activity after intra-PVN microinjections of NMU. After one month of the high-fat diet, however, the obesity-resistant rats showed significantly more NMU-induced physical activity compared to the obese DIO rats. Taken together with previous studies, these results suggest that obesity may represent a state associated with decreased central sensitivity to neuropeptides such as NMU that increase physical activity and therefore energy expenditure.

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The gut–brain peptide neuromedin U is involved in the mammalian circadian oscillator system

Cited by 73 publications

References 43 publications

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice

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

Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity

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