Melanocortin-4 Receptor Messenger Ribonucleic Acid Expression in Rat Cardiorespiratory, Musculoskeletal, and Integumentary Systems

Mountjoy, Kathleen G.; Wu, Chia-Shan; Dumont, Laurence M.; Wild, J. Martin

doi:10.1210/en.2003-0570

Cited by 56 publications

(40 citation statements)

References 59 publications

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“…Absence of salt sensitivity in MC4R (Ϫ/Ϫ) mice suggests that renal MC4R, if present in mice kidneys, does not protect against salt sensitivity of blood pressure. Mountjoy et al 36 reported only mild expression of MC4R in the adult rat kidney, and there have been no studies to our knowledge on renal MC4R expression in mice.…”

Section: Effect Of Hsd (4% Nacl) On Cardiovascular Function In Mc4r (mentioning

confidence: 95%

Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia

et al. 2005

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Abstract-The purpose of this study was to test whether the melanocortin-4 receptor (MC4R) is critical in the development of hypertension associated with obesity and its metabolic disorders. MC4R-deficient homozygous (Ϫ/Ϫ) and heterozygous (ϩ/Ϫ) and wild-type (WT) C57BL/6J mice 17 to 19 weeks old (nϭ5 to 7 per group) were implanted with telemetry devices for monitoring 24-hour mean arterial pressure (MAP) and heart rate (HR). After 3-day stable control measurements on normal-salt diet (NSD; 0.4% NaCl), mice received a high-salt diet (HSD; 4% NaCl) for 7 days, followed by 3-day recovery on NSD. MC4R (Ϫ/Ϫ) mice were severely obese compared with MC4R (ϩ/Ϫ) and WT mice (body weight 48Ϯ1.5 versus 31Ϯ0.6 and 30Ϯ0.5 g respectively). On NSD, MAP was similar in all groups of mice (MC4R (Ϫ/Ϫ) 110Ϯ3 mm Hg; MC4R (ϩ/Ϫ) 109Ϯ2 mm Hg; WT 114Ϯ2 mm Hg), and HR in MC4R (Ϫ/Ϫ) was lower than in WT (604Ϯ5 versus 645Ϯ9 bpm; PϽ0.05) but not different from MC4R (ϩ/Ϫ) (625Ϯ13 bpm) mice. HSD did not significantly alter MAP or HR in any of the groups. Epididymal and retroperitoneal fat weights and plasma leptin levels were several-fold greater in MC4R (Ϫ/Ϫ) compared with MC4R (ϩ/Ϫ) and WT mice. Plasma insulin and glucose levels were also significantly greater in MC4R (Ϫ/Ϫ) than in MC4R (ϩ/Ϫ) and WT mice. These data suggest that despite obesity, visceral adiposity, hyperleptinemia, and hyperinsulinemia, MC4R (Ϫ/Ϫ) mice are neither hypertensive nor salt sensitive, indicating that a functional MC4R may be necessary for the development of hypertension associated with obesity and its metabolic abnormalities. Key Words: obesity Ⅲ insulin resistance Ⅲ hypertension, sodium-dependent Ⅲ arterial pressure Ⅲ renin-angiotensin system E vidence from epidemiological, clinical, and experimental studies has consistently demonstrated that obesity is a major cause of essential hypertension. 1-3 Previous studies show that ␣/␤-adrenergic receptor antagonists and renal denervation significantly blunt the rise in arterial pressure associated with weight gain in diet-induced obese animal models, indicating that increased sympathetic nervous system (SNS) activation is an important cause of obesity-induced hypertension. 3,4 However, the mechanisms that link SNS activation to the development of hypertension in obesity are still unclear.One potential mechanism that could link obesity, SNS activation, and hypertension is the hypothalamic proopiomelanocortin (POMC) pathway. Several studies have indicated that the hypothalamic melanocortin system, acting through the melanocortin-3 receptor (MC3R) and MC4R, is a major regulator of energy balance. ␣-Melanocyte-stimulating hormone (␣-MSH), the proteolytic byproduct of the POMC peptide, activates the hypothalamic MC3/4R to suppress appetite and to increase energy expenditure. 5 Recent studies suggest that the hypothalamic melanocortin system may also be important in cardiovascular regulation. For example, acute intracerebroventricular injections of ␣-MSH increase SNS activity to the kidneys, 6 and chronic activation of MC3/4...

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Section: Effect Of Hsd (4% Nacl) On Cardiovascular Function In Mc4r (mentioning

confidence: 95%

Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia

et al. 2005

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“…It also has protective effects in rat heart ischemia (Guarini et al 2002) and is involved in the anti-inflammatory effects of melanocortins in macrophages (Getting et al 2006). MC4R is expressed predominantly in the brain (Mountjoy et al 1994), although it was also detected in adipose tissue (Chhajlani 1996), in human skin melanocytes (Spencer & Schallreuter 2009), and in rat heart, lung, kidney, and testis (Mountjoy et al 2003). MC5R is widely found in peripheral tissue (Gantz et al 1994, Labbe et al 1994 and has also been detected in some areas of the CNS (Griffon et al 1994).…”

Section: Melanocortin Receptorsmentioning

confidence: 99%

Astrocytes: new targets of melanocortin 4 receptor actions

Caruso¹,

Carniglia²,

Durand³

et al. 2013

Journal of Molecular Endocrinology

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Astrocytes exert a wide variety of functions with paramount importance in brain physiology. After injury or infection, astrocytes become reactive and they respond by producing a variety of inflammatory mediators that help maintain brain homeostasis. Loss of astrocyte functions as well as their excessive activation can contribute to disease processes; thus, it is important to modulate reactive astrocyte response. Melanocortins are peptides with well-recognized anti-inflammatory and neuroprotective activity. Although melanocortin efficacy was shown in systemic models of inflammatory disease, mechanisms involved in their effects have not yet been fully elucidated. Central anti-inflammatory effects of melanocortins and their mechanisms are even less well known, and, in particular, the effects of melanocortins in glial cells are poorly understood. Of the five known melanocortin receptors (MCRs), only subtype 4 is present in astrocytes. MC4R has been shown to mediate melanocortin effects on energy homeostasis, reproduction, inflammation, and neuroprotection and, recently, to modulate astrocyte functions. In this review, we will describe MC4R involvement in anti-inflammatory, anorexigenic, and anti-apoptotic effects of melanocortins in the brain. We will highlight MC4R action in astrocytes and discuss their possible mechanisms of action. Melanocortin effects on astrocytes provide a new means of treating inflammation, obesity, and neurodegeneration, making them attractive targets for therapeutic interventions in the CNS.

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“…The central melanocortin system appears to be an important mediator of the actions of both leptin and insulin (Seeley et al 1997, 2005, Williams et al 2001, Benoit et al 2002, which are key elements in the control of energy balance (Friedman 2002, Schneider et al 2002, Small et al 2002, Matsumura et al 2003, Mountjoy et al 2003, Pankov Iu 2005. Experimental blockade of melanocortin receptors (MCRs) in mice suppresses the ability of both leptin and insulin to reduce food intake and enhance weight loss (Benoit et al 2002, Seeley et al 2005.…”

Section: Introductionmentioning

confidence: 99%

The melanocortin circuit in obese and lean strains of chicks

Hen

Yosefi

Simchaev

et al. 2006

Journal of Endocrinology

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Agonists of membranal melanocortin 3 and 4 receptors (MC3/4Rs) are known to take part in the complex control mechanism of energy balance. In this study, we compared the physiological response to an exogenous MC3/4R agonist and the hypothalamic expression of proopic melanocortin (POMC) gene, encoding few MC3/4R ligands, between broiler and layer chicken strains. These strains, representing the two most prominent commercial strains of chickens grown for meat (broilers) and egg production (layers), differ in their food intake, fat accumulation, and reproductive performance and, therefore, form a good model of obese and lean phenotypes, respectively. A single i.v. injection of the synthetic peptide melanotan-II (MT-II; 1 mg/kg body weight) into the wing vein of feed-restricted birds led to attenuation of food intake upon exposure to feeding ad libitum in both broiler and layer chickens. A study of the POMC mRNA encoding the two prominent natural MC3/4R agonists, a-MSH and ACTH, also revealed a general similarity between the strains. Under feeding conditions ad libitum, POMC mRNA levels were highly similar in chicks of both strains and this level was significantly reduced upon feed restriction. However, POMC mRNA down-regulation upon feed restriction was more pronounced in layers than in broilers. These results suggest: (i) a role for MC3/4R agonists in the control of appetite; (ii) that the physiological differences between broilers and layers are not related to unresponsiveness of broiler chickens to the satiety signal of MC3/4R ligands. Therefore, these findings suggest that artificial activation of this circuit in broiler chicks could help to accommodate with their agricultural shortcomings of overeating, fattening, and impaired reproduction.

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Melanocortin-4 Receptor Messenger Ribonucleic Acid Expression in Rat Cardiorespiratory, Musculoskeletal, and Integumentary Systems

Cited by 56 publications

References 59 publications

Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia

Melanocortin-4 Receptor–Deficient Mice Are Not Hypertensive or Salt-Sensitive Despite Obesity, Hyperinsulinemia, and Hyperleptinemia

Astrocytes: new targets of melanocortin 4 receptor actions

The melanocortin circuit in obese and lean strains of chicks

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