Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats

Shearman, Lauren P.; Camacho, Ramon; Stribling, Donald; Zhou, Dan; Bednarek, Maria A.; Hreniuk, Donna L.; Feighner, Scott D.; Tan, Carina P.; Howard, Andrew D.; Ploeg, Lex H.T. Van der; MacIntyre, D. Euan; Hickey, Gerard J.; Strack, Alison M.

doi:10.1016/s0014-2999(03)02146-0

Cited by 164 publications

(121 citation statements)

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“…In the recent years, several MCH1-R antagonists such as T-226296 [27], SNAP-7941 [4] or the antagonist characterized by Bednarek et al [1], Shearman et al [23] and Mashiko et al [18] have been developed. These drugs significantly reduce MCH-induced increase in food intake when MCH is injected centrally and the antagonist is given orally (T-226296, [27]), intraperitoneally (SNAP-7941, [4]) or intracerebroventrically [18,23].…”

Section: Introductionmentioning

confidence: 99%

“…These drugs significantly reduce MCH-induced increase in food intake when MCH is injected centrally and the antagonist is given orally (T-226296, [27]), intraperitoneally (SNAP-7941, [4]) or intracerebroventrically [18,23].…”

Section: Introductionmentioning

confidence: 99%

“…First, there is controversy regarding the effect of MCH on water intake. Shearman et al [23] showed that MCH influences food intake without affecting water intake while Clegg et al [9] demonstrated that central injections of MCH into the third ventricle stimulated both food intake and water intake. In the latter studies, when food was not available, MCH still stimulated water intake.…”

Section: Introductionmentioning

confidence: 99%

“…Chronic treatment with an MCH1-R antagonist alters appetite, body weight and adiposity in Sprague -Dawley rats [23] and in diet-induced obese (DIO) mice [18]. In addition, Borowsky et al [4] showed that the MCH1-R antagonist SNAP-7941 injected intraperitoneally would block the intake a highly palatable food (sweet condensed milk).…”

Section: Introductionmentioning

confidence: 99%

“…In the first series of experiments, we investigated, in rats given either lab chow or a medium high fat diet, whether feeding induced by central administration of MCH could be blocked by central injections of a MCH1-R antagonist peptide (corresponding to Compound 30 in Bednarek et al [1] and to Compound B in Shearman et al [23]). In the next series of experiments, we investigated whether the MCH1-R antagonist blocked MCH-induced water intake.…”

Section: Introductionmentioning

confidence: 99%

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Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Morens

Nørregaard²,

Receveur³

et al. 2005

Brain Research

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Receveur, J-M. (2005). Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake. Brain-research, 1062(1-2), 32-38. DOI: 10.1016DOI: 10. /j.brainres.2005 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractMelanin concentrating hormone (MCH) is a regulator of ingestive behavior, but several issues regarding its effects on specific components of ingestive behavior remain to be elucidated. Therefore, we injected, in the 3rd ventricle of male Wistar rats, saline, MCH (5 Ag), MCH (5 Ag) together with a MCH1-R antagonist (A, 10 Ag) and the antagonist alone (A, 10 Ag). Our results show that (1) central administration of MCH stimulates food intake (lab chow and medium high fat diet) and this can be blocked by a MCH1-R antagonist; (2) the MCH-induced increase in food intake is mediated through increased meal number, meal duration and meal size; (3) the MCH1-R antagonist is able to significantly reduce the intake of a highly palatable food (condensed sweet milk) and is more effective in blocking MCH-induced food intake when rats are fed a palatable medium high fat food; and (4) MCH stimulated water intake independently from and disproportionately to food intake. In conclusion, our results point to an involvement of endogenous MCH in the enhanced intake of palatable food. Furthermore, they confirm that MCH stimulates not only food intake but also water intake. D

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Morens

Nørregaard²,

Receveur³

et al. 2005

Brain Research

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Neurochemical characterization of neurons expressing melanin‐concentrating hormone receptor 1 in the mouse hypothalamus

Chee

Pissios

Maratos–Flier

2013

J of Comparative Neurology

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Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts via MCH receptor 1 (MCHR1) in the mouse. It promotes positive energy balance thus mice lacking MCH or MCHR1 are lean, hyperactive, and resistant to diet-induced obesity. Identifying the cellular targets of MCH is an important step to understanding the mechanisms underlying MCH actions. We generated the Mchr1-cre mouse that expressed cre recombinase driven by the MCHR1 promoter and crossed it with a tdTomato reporter mouse. The resulting Mchr1-cre/tdTomato progeny expressed easily detectable tdTomato fluorescence in MCHR1 neurons, which were found throughout the olfactory system, striatum, and hypothalamus. To chemically identify MCH-targeted cell populations that play a role in energy balance, MCHR1 hypothalamic neurons were characterized by colabeling select hypothalamic neuropeptides with tdTomato fluorescence. TdTomato fluorescence colocalized with dynorphin, oxytocin, vasopressin, enkephalin, thyrothropin-releasing hormone, and corticotropin-releasing factor immunoreactive cells in the paraventricular nucleus. In the lateral hypothalamus, neurotensin but neither orexin nor MCH neurons expressed tdTomato. In the arcuate nucleus, both Neuropeptide Y and proopiomelanocortin cells expressed tdTomato. We further demonstrated that some of these arcuate neurons were also targets of leptin action. Interestingly, MCHR1 was expressed in the vast majority of leptin-sensitive proopiomelanocortin neurons, highlighting their importance for the orexigenic actions of MCH. Taken together, this study supports the use of the Mchr1-cre mouse for outlining the neuroanatomical distribution and neurochemical phenotype of MCHR1 neurons.

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A CreER mouse to study melanin concentrating hormone signaling in the developing brain

Engle

Antonellis

Whitehouse

et al. 2018

Genesis

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The neuropeptide, melanin concentrating hormone (MCH), and its G protein-coupled receptor, melanin concentrating hormone receptor 1 (Mchr1), are expressed centrally in adult rodents. MCH signaling has been implicated in diverse behaviors such as feeding, sleep, anxiety, as well as addiction and reward. While a model utilizing the Mchr1 promoter to drive constitutive expression of Cre recombinase (Mchr1-Cre) exists, there is a need for an inducible Mchr1-Cre to determine the roles for this signaling pathway in neural development and adult neuronal function. Here, we generated a BAC transgenic mouse where the Mchr1 promotor drives expression of tamoxifen inducible CreER recombinase. Many aspects of the Mchr1-Cre expression pattern are recapitulated by the Mchr1-CreER model, though there are also notable differences. Most strikingly, compared to the constitutive model, the new Mchr1-CreER model shows strong expression in adult animals in hypothalamic brain regions involved in feeding behavior but diminished expression in regions involved in reward, such as the nucleus accumbens. The inducible Mchr1-CreER allele will help reveal the potential for Mchr1 signaling to impact neural development and subsequent behavioral phenotypes, as well as contribute to the understanding of the MCH signaling pathway in terminally differentiated adult neurons and the diverse behaviors that it influences.

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Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats

Cited by 164 publications

References 40 publications

Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Effects of MCH and a MCH1-receptor antagonist on (palatable) food and water intake

Neurochemical characterization of neurons expressing melanin‐concentrating hormone receptor 1 in the mouse hypothalamus

A CreER mouse to study melanin concentrating hormone signaling in the developing brain

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