Neuromedin U and Neuromedin U receptor‐2 expression in the mouse and rat hypothalamus: effects of nutritional status

Graham, Scott E.; Turnbull, Yvonne; Fotheringham, P; Nilaweera, Kanishka N.; Mercer, Julian G.; Morgan, Peter J.; Barrett, Perry

doi:10.1046/j.1471-4159.2003.02079.x

Cited by 96 publications

(149 citation statements)

References 26 publications

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“…210 Like the MC4-R and Y1-R, a subtype of NMU receptors is expressed in the rat hypothalamus. 211,212 If and how NMU affects CNS systems regulating emotion and behavior remain open to future analysis. Moreover, there are undoubtedly other molecules that will be discovered and may serve as links between obesity and psychiatry research.…”

Section: Discussionmentioning

confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

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Regulated energy homeostasis is fundamental for maintaining life. Unfortunately, this critical process is affected in a high number of mentally ill patients. Eating disorders such as anorexia nervosa are prevalent in modern societies. Impaired appetite and weight loss are common in patients with depression. In addition, the use of neuroleptics frequently produces obesity and diabetes mellitus. However, the neural mechanisms underlying the pathophysiology of these behavioral and metabolic conditions are largely unknown. In this review, we first concentrate on the established brain machinery of food intake and body weight, especially on the melanocortin and neuropeptide Y (NPY) systems as illustration. These systems play a critical role in receiving and processing critical peripheral metabolic cues such as leptin and ghrelin. It is also notable that both systems modulate emotion and motivated behavior as well. Secondly, we discuss the significance and potential promise of multidisciplinary molecular and neuroanatomic techniques that will likely increase the understanding of brain circuitries coordinating energy homeostasis and emotion. Finally, we introduce several lines of evidence suggesting a link between the melanocortin/NPY systems and several neurotransmitter systems on which many of the psychotropic agents exert their influence. Maintaining energy homeostasis is fundamental for survival. However, obesity due to over-nutrition is an increasing worldwide public health problem. 1 In psychiatric practice, on the other hand, impaired appetite is one of the crucial issues. Anorexia and weight loss are common, for example, in patients suffering from depression. Eating disorders are medically intractable and life threatening. In addition, the so-called 'atypical' antipsychotic agents, currently and widely used to treat psychoses, often induce hyperphagia, obesity, and diabetes mellitus. [2][3][4] In the past decade, fortunately, there has been remarkable progress in understanding the molecular mechanisms of food intake and body weight. This is due in large part to increased research activity towards combating the rising incidences of obesity and associated metabolic disorders. As a result, it is now established that the central nervous system (CNS) senses and processes peripheral metabolic cues including leptin 5 and ghrelin, 6,7 resulting in coordinated energy homeostasis. However, the pathophysiology of the disequilibrium between energy intake and expenditure in psychiatric disorders remains largely unknown. Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to...

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Section: Discussionmentioning

confidence: 99%

Body weight is regulated by the brain: a link between feeding and emotion

2005

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“…It is a highly conserved molecule existing in two molecular forms: an octapeptide (NMU-8) constituting the core active C terminus and complete 25 amino acid peptide, NMU-25 (Minamino et al 1985). In the mouse central nervous system, NMU is expressed in the suprachiasmatic (SCN), dorsomedial (DMH), ventromedial (VMH) and arcuate nuclei of the hypothalamus (Graham et al 2003). These nuclei are important in controlling circadian rhythms, appetite and energy balance (Takahashi & Zatz 1982, Williams et al 2001.…”

Section: Introductionmentioning

confidence: 99%

“…These nuclei are important in controlling circadian rhythms, appetite and energy balance (Takahashi & Zatz 1982, Williams et al 2001. In contrast, NMU expression in the rat is limited to the SCN, relatively few diffuse cells in the arcuate nuclei and DMH in the hypothalamus and the nuclei of the solitary tract (NTS) and the inferior olive in the brainstem (Ivanov et al 2002, Graham et al 2003. However, relatively high levels of NMU are found in the pars tuberalis of the pituitary, which adheres closely to the ventral edge of the hypothalamic median eminence (Ivanov et al 2002, Graham et al 2003.…”

Section: Introductionmentioning

confidence: 99%

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Nogueiras¹,

Tovar²,

Mitchell³

et al. 2006

Journal of Endocrinology

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Central neuromedin U (NMU) functions in energy balance, the hypothalamic-pituitary-adrenal axis, LH release and circadian rhythmicity. In rats, high levels of NMU occur in the hypothalamic suprachiasmatic nuclei and the pars tuberalis of the pituitary. NMU expression in the pars tuberalis appears to be downregulated in the Zucker fatty (fa/fa) rat, lacking functional leptin receptors. In contrast, in the dorsomedial (DMH) nuclei of the mouse, NMU expression is higher in the ob/ob mouse, lacking leptin, and is upregulated by fasting. However, leptin appears not to change NMU gene expression in either the mouse DMH or the rat pars tuberalis. Thus, the present study aims to better identify factors influencing central NMU expression in the rat pars tuberalis. SpragueDawley rats were fasted and/or challenged with intracerebroventricular leptin or ghrelin and gene expression was measured using real-time reverse transcriptase-PCR and quantitative in situ hybridisation with riboprobes specific for NMU and NMU receptor (NMU-R2). NMU expression in the rat pars tuberalis was elevated by fasting. Ghrelin administration had no effect on the level of NMU expression, but leptin was found to diminish the expression in a concentration-and time-dependent manner. NMU-R2 expression was unchanged in any of the groups measured. These results suggest that NMU expression in rat pars tuberalis is upregulated in states of negative energy balance, and this may be mediated indirectly by changes in leptin levels. These results demonstrate a link between energy balance and NMU expression in the pars tuberalis of the pituitary.

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“…NPY, cholecystokinin, galanin, leptin, orexins, beacon and NPW) (11)(12)(13)(14)(15)(16)(17), also NMU appears to regulate the hypothalamic-pituitary-adrenal (HPA) axis. The expression of NMU and NMUR 2 was found in the hypothalamus and anterior pituitary (10,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), while in the adrenal glands only the expression of NMUR1 was detected (9,(27)(28)(29)33,34). NMU has been shown to enhance c-fos expression in the hypothalamic paraventricular nucleus (1,2,30,35), to increase CRH and vasopressin output from rat hypothalamic explants, and to stimulate ACTH and corticosterone secretion in the rat (2,4,5,(36)(37)(38).…”

Section: Introductionmentioning

confidence: 96%

“…8). NMU acts via two subtypes of G protein-coupled receptors, NMUR1 and NMUR2, the former being the peripheral receptor and the latter the central one (9,10).…”

Section: Introductionmentioning

confidence: 99%

Effects of neuromedin-U on immature rat adrenocortical cells: In vitro and in vivo studies

Ziółkowska¹,

Macchi²,

Trejter³

et al. 2008

Int J Mol Med

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Abstract. Neuromedin U (NMU) is a brain-gut peptide, that in the peripheral organs and tissues acts via a G protein-coupled receptor, called NMUR1. Reverse transcription-polymerase chain reaction showed the expression of NMUR1 mRNA in either cortex and medulla or dispersed zona glomerulosa and zona fasciculata-reticularis cells of the immature rat adrenals. Accordingly, immunocytochemistry demonstrated the presence of NMUR1-like immunoreactivity in the cortex and medulla of immature adrenals. NMU8 administration to immature rats was found to raise aldosterone, but not corticosterone, plasma concentration, without altering adrenal growth. Conversely, the exposure to NMU8 markedly enhanced the proliferative activity of immature rat inner adrenocortical cells in primary in vitro culture, without significantly affecting their corticosterone secretion. Collectively, our findings suggest that adrenals of immature rats may be a target for circulating NMU. However, the physiological significance and relevance of the adrenal effects of NMU remain to be ascertained.

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Neuromedin U and Neuromedin U receptor‐2 expression in the mouse and rat hypothalamus: effects of nutritional status

Cited by 96 publications

References 26 publications

Body weight is regulated by the brain: a link between feeding and emotion

Body weight is regulated by the brain: a link between feeding and emotion

Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Effects of neuromedin-U on immature rat adrenocortical cells: In vitro and in vivo studies

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