The Role of Melanin-Concentrating Hormone and Its Receptors in Energy Homeostasis

MacNeil, Douglas J.

doi:10.3389/fendo.2013.00049

Cited by 72 publications

(60 citation statements)

References 134 publications

(231 reference statements)

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“…Similarly, in the hypothalami of Bbs2 − / − and Bbs4 − / − mice, ACIII + cilia appear normal in number and length; however, neither SSTR3 nor MCHR1 is recruited to neuronal cilia . Several studies have shown a role for MCH, MCH + neurons, and MCHR1 in energy homeostasis . On the other hand, loss of function renders the mice resistant to diet‐induced obesity (DIO) and does not result in hyperphagia or increased fat mass.…”

Section: Primary Ciliary Function and Obesitymentioning

confidence: 99%

“…43 Several studies have shown a role for MCH, MCH + neurons, and MCHR1 in energy homeostasis. 44 On the other hand, loss of function renders the mice resistant to diet-induced obesity (DIO) and does not result in hyperphagia or increased fat mass. Consequently, it is not clear how a lack of ciliary MCHR1 would contribute to obesity, assuming that ciliary localization is necessary for proper MCHR1 function.…”

Section: Primary Ciliary Function and Obesitymentioning

confidence: 99%

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The role of primary cilia in obesity and diabetes

Volta

Gerdes

2016

Annals of the New York Academy of Sciences

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One in 12 people worldwide suffers from diabetes and more than 90% of affected adult individuals are diagnosed with type 2 diabetes mellitus (T2DM). Obesity adds to the personal risk to develop T2DM, and both metabolic diseases are rampantly increasing worldwide. Over recent years, primary cilia have moved into the focus of basic and clinical research, after several human diseases have been identified as ciliopathies (i.e., they are linked to ciliary dysfunction). A subset of ciliopathies presents with obesity and diabetes, either as core symptoms or major complications. Several studies have shown a role for ciliary signaling in the satiety signaling centers of the hypothalamus and in other metabolically active tissues, such as pancreatic islets. Here, we discuss recent advances and perspectives in ciliary metabolic research.

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Section: Primary Ciliary Function and Obesitymentioning

confidence: 99%

Section: Primary Ciliary Function and Obesitymentioning

confidence: 99%

The role of primary cilia in obesity and diabetes

Volta

Gerdes

2016

Annals of the New York Academy of Sciences

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“…To better understand the role of MCH-MCHR1 system in energy homeostasis, several structurally distinct small molecule antagonists for the MCHR1 have been synthesized and tested in cell-based assays for their selectivity and for in vivo potency in the rodent. Comprehensive review of desired selectivity and efficacy of MCHR1 antagonist in vivo should consult some recent reviews (38, 39). The majority of studies indicated that the MCHR1 antagonists are effective in different models of obesity in a variety of different rodent strains, due to inhibition of food intake and/or energy expenditure (40, 41).…”

Section: Mch Acts Through Gpcrsmentioning

confidence: 99%

Regulated Control of Melanin-Concentrating Hormone Receptor 1 through Posttranslational Modifications

2013

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Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays an important role in feeding behavior. It activates two G-protein-coupled receptors, MCHR1 and MCHR2, of which MCHR1 is the primary regulator of food intake and energy homeostasis in rodents. In mammalian cells transfected with MCHR1, MCH is able to activate multiple signaling pathways including calcium mobilization, extracellular signal-regulated kinase activation, and inhibition of cyclic AMP generation through Gi/o- and Gq-coupled pathways. Further evidence suggests that MCHR1 is regulated through posttranslational modifications, which control its intracellular localization and provide appropriate cellular responses involving G-protein signaling. This review summarizes the current data on the control of MCHR1 function through glycosylation and phosphorylation, as related to cell function. Especially, a series of mutagenesis study highlights the importance of complete glycosylation of MCHR1 for efficient trafficking to the plasma membrane.

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“…Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that consists of 19 amino acids, derived from a 165-amino acid preprohormone encoded by the Pmch gene. MCH exerts its effects through MCHR1 and MCHR2 receptors, which are also G protein-coupled receptors [1112]. MCH neurons are distributed adjacent to orexin neurons in the lateral hypothalamus, and MCH neurons also project throughout the brain [1314].…”

Section: Introductionmentioning

confidence: 99%

Functional Connectivity of Basolateral Amygdala Neurons Carrying Orexin Receptors and Melanin-concentrating Hormone Receptors in Regulating Sociability and Mood-related Behaviors

Kim

Han

2016

Exp Neurobiol

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Chronic stress induces changes in neuronal functions in specific brain regions regulating sociability and mood-related behaviors. Recently we reported that stress-induced persistent upregulation of the neuropeptides orexin and melanin-concentrating hormone (MCH) in the basolateral amygdala (BLA) and the resulting activation of orexin receptors or MCH receptors within the BLA produced deficits in sociability and mood-related behaviors. In the present study, we investigated the neural targets that were innervated by BLA neurons containing orexin receptors or MCH receptors. The viral vector system AAV2-CaMKII-ChR2-eYFP was injected into the BLA to trace the axonal tracts of BLA neurons. This axon labeling analysis led us to identify the prelimbic and infralimbic cortices, nucleus accumbens (NAc), dorsal striatum, paraventricular nucleus (PVN), interstitial nucleus of the posterior limb of the anterior commissure, habenula, CA3 pyramidal neurons, central amygdala, and ventral hippocampus as the neuroanatomical sites receiving synaptic inputs of BLA neurons. Focusing on these regions, we then carried out stimulus-dependent c-Fos induction analysis after activating orexin receptors or MCH receptors of BLA neurons. Stereotaxic injection of an orexin receptor agonist or an MCH receptor agonist in the BLA induced c-Fos expression in the NAc, PVN, central amygdala, ventral hippocampus, lateral habenula and lateral hypothalamus, which are all potentially important for depression-related behaviors. Among these neural correlates, the NAc, PVN and central amygdala were strongly activated by stimulation of orexin receptors or MCH receptors in the BLA, whereas other BLA targets were differentially and weakly activated. These results identify a functional connectivity of BLA neurons regulated by orexin and MCH receptor systems in sociability and mood-related behaviors.

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The Role of Melanin-Concentrating Hormone and Its Receptors in Energy Homeostasis

Cited by 72 publications

References 134 publications

The role of primary cilia in obesity and diabetes

The role of primary cilia in obesity and diabetes

Regulated Control of Melanin-Concentrating Hormone Receptor 1 through Posttranslational Modifications

Functional Connectivity of Basolateral Amygdala Neurons Carrying Orexin Receptors and Melanin-concentrating Hormone Receptors in Regulating Sociability and Mood-related Behaviors

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