Expression of the melanin‐concentrating hormone (MCH) receptor mRNA in the rat brain

Saito, Yumiko; Cheng, Michelle Y.; Leslie, Frances M.; Civelli, Olivier

doi:10.1002/cne.1191

Cited by 358 publications

(301 citation statements)

References 61 publications

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“…Conversely, a similar phenomenon could also be deduced for MCHergic synaptic innervation of ORX-containing neurons as many MCH receptors have been found in the LH. 17 Orexin -MCH synaptic interactions in feeding regulation To date, it has been demonstrated that ORX is involved in many physiological phenomena including food intake, 27 -30 sleep, 31 -33 endocrine function, 34 -37 narcolepsy 38,39 and regulation of body temperature, 40 muscle tone 41 and even pain sensation. 42 Likewise, MCH has been shown to play a role in food intake, 5 -7 endocrine function 43 -46 and pigmentation.…”

Section: Orexin -Mch Synaptic Interactionsmentioning

confidence: 99%

“…Given that both MCH-and ORX-containing neurons are involved in the regulation of food-intake behavior, one may imagine the possibility of direct synaptic relationships between them. Furthermore, ORX 16 and MCH 17 receptors have been found in the LH. The findings increase the possibility of reciprocal synaptic relationships between the ORX-and MCH-containing neurons.…”

Section: Introductionmentioning

confidence: 99%

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Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus: a novel circuit implicated in feeding regulation

Uehara

et al. 2002

Int J Obes

116

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OBJECTIVE: Both orexin (ORX)-and melanin-concentrating hormone (MCH) are expressed in different neurons in the lateral hypothalamic area (LH), and are considered to have common effects on stimulating food intake. There are no reports to demonstrate neural interactions between them at the ultrastructural level. We observed these neurons in the LH to evaluate the relationships between them. DESIGN: We used two different types of double immunostaining to reveal the ultrastructure of both the ORX-and MCHcontaining neurons. A preembedding double immunostaining technique was used to study the synaptic relationships between the two kinds of neuron. RESULTS: The main new findings are as follows: 1) Both ORX-and MCH-containing neurons received other synaptic input and made synaptic input to other neurons; 2) Reciprocal synaptic relationships were observed between the ORX-and MCHcontaining neurons. CONCLUSION: The ORX-and MCH-containing neurons in the lateral hypothalamic area may influence food intake through synapse with each other.

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Section: Orexin -Mch Synaptic Interactionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus: a novel circuit implicated in feeding regulation

Uehara

et al. 2002

Int J Obes

116

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“…Pmch mRNA is upregulated after fasting or leptin deficiency (32, 50); third ventricle intracerebroventricular injections of MCH increase food intake and body weight (11,19,22,28,53); Pmch knockout mice are lean due to a decreased food intake and an increased metabolic rate (31, 59); and overexpression of MCH causes obesity (35). In rodents MCH binds to melanin-concentrating hormone receptor 1 (MCH1R), a G protein-coupled receptor expressed throughout the brain (7,33,55,56). MCH1R is particularly enriched in the nucleus accumbens shell (33,47,56), thus forming a potential hypothalamiclimbic circuit modulating the hedonic, or rewarding, aspects of feeding (16, 47).…”

mentioning

confidence: 99%

Pmchexpression during early development is critical for normal energy homeostasis

Mul

Berg³

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Mul JD, Yi CX, van den Berg SAA, Ruiter M, Toonen PW, van der Elst MCJ, Voshol PJ, Ellenbroek BA, Kalsbeek A, la Fleur SE, Cuppen E. Pmch expression during early development is critical for normal energy homeostasis. Am J Physiol Endocrinol Metab 298: E477-E488, 2010. First published November 24, 2009 doi:10.1152/ajpendo.00154.2009.-Postnatal development and puberty are times of strong physical maturation and require large quantities of energy. The hypothalamic neuropeptide melanin-concentrating hormone (MCH) regulates nutrient intake and energy homeostasis, but the underlying mechanisms are not completely understood. Here we use a novel rat knockout model in which the MCH precursor Pmch has been inactivated to study the effects of loss of MCH on energy regulation in more detail. Pmch Ϫ/Ϫ rats are lean, hypophagic, osteoporotic, and although endocrine parameters were changed in pmch Ϫ/Ϫ rats, endocrine dynamics were normal, indicating an adaptation to new homeostatic levels rather than disturbed metabolic mechanisms. Detailed body weight growth and feeding behavior analysis revealed that Pmch expression is particularly important during early rat development and puberty, i.e., the first 8 postnatal weeks. Loss of Pmch resulted in a 20% lower set point for body weight that was determined solely during this period and remained unchanged during adulthood. Although the final body weight is diet dependent, the Pmch-deficiency effect was similar for all diets tested in this study. Loss of Pmch affected energy expenditure in both young and adult rats, although these effects seem secondary to the observed hypophagia. Our findings show an important role for Pmch in energy homeostasis determination during early development and indicate that the MCH receptor 1 system is a plausible target for childhood obesity treatment, currently a major health issue in first world countries. melanin-concentrating hormone; hypothalamus; childhood obesity; rat knockout model CHILDHOOD OBESITY IS NOW WIDELY recognized as a severe public health issue (43). Treatment with drugs aimed at neural systems involved in the determination of the energy balance could potentially result in a lower energy balance during puberty as well as later in adulthood. Therefore, neuropeptides involved in body weight regulation during early development and puberty are attractive targets for anti-childhood obesity drugs.The neuronal metabolic systems in humans and primates develop prenatally, while in rodents these systems develop during the first 3 postnatal weeks (5, 21). This results in the activation and optimization of neuronal systems during early rodent development. A second important metabolic period is puberty, a period of major growth, hormonal changes, and sexual maturation. In the rat, puberty is characterized by different responses of young-adolescent [postnatal day (PND) 40] and young-adult (PND 60) male rats to environmental cues like stress and cold (17,18). In addition to these age-dependent behavioral differences, the amount of food consumed durin...

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“…In the rodent brain, MCHR1 is expressed in areas important for feeding, learning and motivated behavior, integration of sensory and gustatory inputs, autonomic control, and arousal (22,23). MCHR1 mRNA is also expressed in the thyroid, kidney, adipose tissue, lung, testes, and tongue (23), whereas functional MCHR1 is also present in lymphocytes (12,14), insulin-producing cell lines (24), and mouse and human pancreatic islets (8).…”

mentioning

confidence: 99%

Melanin-concentrating hormone as a mediator of intestinal inflammation

Kokkotou¹,

Moss²,

Torres³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Melanin-concentrating hormone (MCH) is expressed primarily in the hypothalamus and has a positive impact on feeding behavior and energy balance. Although MCH is expressed in the gastrointestinal tract, its role in this system remains elusive. We demonstrate that, compared to wild type, mice genetically deficient in MCH had substantially reduced local inflammatory responses in a mouse model of experimental colitis induced by intracolonic administration of 2,4,6 trinitrobenzene sulfonic acid (TNBS). Likewise, mice receiving treatments with an anti-MCH antibody, either prophylactically or after the establishment of colitis, developed attenuated TNBS-associated colonic inflammation and survived longer. Consistent with a potential role of MCH in intestinal pathology, we detected increased colonic expression of MCH and its receptor in patients with inflammatory bowel disease. Moreover, we found that human colonic epithelial cells express functional MCH receptors, the activation of which induces IL-8 expression. Taken together, these results clearly implicate MCH in inflammatory processes in the intestine and perhaps elsewhere.experimental colitis ͉ IL-8 ͉ inflammatory bowel disease ͉ neuropeptides ͉ MCH deficient mice M elanin-concentrating hormone (MCH) is a 17-to 19-aa cyclic neuropeptide conserved from fish to human (1) and predominantly localized in the brain (2). Several pharmacological and genetic studies revealed a role for this peptide in the regulation of feeding behavior and energy expenditure toward a positive energy balance (3-5). More recent studies extended the physiological functions of MCH as a broad regulator of cognitive and autonomic aspects related to rewarding behaviors (6, 7). Outside the brain, MCH is localized in the pancreas (8), skin (9), and gastrointestinal tract (10). It has been also found in tissular and circulating immune cells (11)(12)(13)(14). However, the physiological role of MCH in these peripheral tissues has yet to be established.In humans, two G-protein-coupled receptors for MCH have been identified, MCHR1 (also known as SLC1 or GPR24) (15-18) and MCHR2 (19-21), whereas rodents express only MCHR1. In the rodent brain, MCHR1 is expressed in areas important for feeding, learning and motivated behavior, integration of sensory and gustatory inputs, autonomic control, and arousal (22, 23). MCHR1 mRNA is also expressed in the thyroid, kidney, adipose tissue, lung, testes, and tongue (23), whereas functional MCHR1 is also present in lymphocytes (12,14), insulin-producing cell lines (24), and mouse and human pancreatic islets (8).Several neuropeptides that are part of the neuroendocrine system exhibit important immunomodulatory effects and mediate inflammation in various organs, including the intestine (25, 26). There is little evidence to indicate expression of MCHR of either type in the intestine of animals or humans, and the role of MCH in inflammatory responses in the gut or elsewhere has not been evaluated. Based on these considerations and because MCH is also expressed in immune c...

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Expression of the melanin‐concentrating hormone (MCH) receptor mRNA in the rat brain

Cited by 358 publications

References 61 publications

Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus: a novel circuit implicated in feeding regulation

Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus: a novel circuit implicated in feeding regulation

Pmchexpression during early development is critical for normal energy homeostasis

Melanin-concentrating hormone as a mediator of intestinal inflammation

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