The role of melanocortin neuronal pathways in circadian biology: a new homeostatic output involving melanocortin‐3 receptors?

Begriche, Karima; Sutton, Gregory M.; Fang, Jidong; Butler, Andrew A.

doi:10.1111/j.1467-789x.2009.00662.x

Cited by 18 publications

(17 citation statements)

References 116 publications

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“…The MC3-R −/− mouse is resistant to the induction of natriuresis by γ-MSH, is sensitive to hypertension induced by a high-salt diet, and displays defects in circadian rhythms (17,18). During the course of our studies on obesity in the MC3-R −/− mouse, we found that, although lipogenesis appeared normal, fasting-induced mobilization of fatty acids from adipose tissue was blunted.…”

mentioning

confidence: 78%

Melanocortin-3 receptor regulates the normal fasting response

Renquist

Murphy

Larson

et al. 2012

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

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The melanocortin-3 receptor-deficient (MC3-R −/− ) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R −/− mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R −/− mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. energy homeostasis | nonesterified fatty acid | corticotrophin-releasing hormone | hormone-sensitive lipase R esearch on the central melanocortin system has focused on the role of the melanocortin-4 receptor (MC4-R) in energy homeostasis, particularly as a result of the hyperphagic obesity syndrome found in both mice and humans with mutations in this receptor (1-3). A large body of work has demonstrated that circuitry regulated by the MC4-R is essential for much of leptin action and coordinates energy intake with energy expenditure to maintain long-term energy homeostasis (4). In contrast, the melanocortin-3 receptor (MC3-R), expressed in ∼35 different nuclei in the CNS with a pattern distinct from that of the MC4-R

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mentioning

confidence: 78%

Melanocortin-3 receptor regulates the normal fasting response

Renquist

Murphy

Larson

et al. 2012

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

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“…43 Furthermore, the ability to synchronize rhythms of increased vigilance and food-seeking behaviours that anticipate nutrient GPCRs in energy homeostasis/balance N Gallo-Payet consumption requires functional MC3R. 15,16,18,43,44 The results from Begriche et al 15,16,45 suggest that MC3Rs modulate the expression of the 'anticipatory' response to nutrients. Mc3r À/À mice subjected to daily RF regimes in which 60--70% of normal caloric intake is presented mid-light cycle or at 24-h intervals in constant dark exhibit attenuated 'food anticipatory activity'.…”

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confidence: 92%

“…39--41 The laboratory of Andrew Butler has focused on a role for MC3R in the expression of circadian rhythms in anticipatory behaviour. 15,16,42 Restricted feeding (RF) paradigms with a periodicity of 24 h rapidly induce entrainment of rhythms anticipating food presentation that are independent of master clocks in the suprachiasmatic nucleus but do require other hypothalamic structures. Sutton et al 43 reported that the melanocortin system is required for the expression of food-entrainable rhythms.…”

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confidence: 99%

“…On the basis of observations from studies examining daily rhythms in rats with various hypothalamic lesions, Andrew Butler hypothesizes that the melanocortin system acts through the Mc3r to link signals of energy status with the system expressing rhythms of food anticipatory behaviour. 16 Clocks integrate cues from environmental and systemic signals of energy status to regulate diverse cellular and physiological functions. The integration of the circadian clock and energy metabolism is controlled by biological signals at multiple levels.…”

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confidence: 99%

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Central (mainly) actions of GPCRs in energy homeostasis/balance: view from the Chair

Gallo‐Payet

2014

Int J Obes Supp

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To maintain a constant body weight, energy intake must equal energy expenditure; otherwise, there is a risk of overweight and obesity. The hypothalamus is one of the primary brain regions where multiple nutrient-related signals from peripheral and central sources converge and become integrated to regulate both short-and long-term nutritional states. The aim of the afternoon session of the 15th Annual International Symposium of the Laval University Obesity Research Chair held in Quebec City on 9 November 2012 was to present the most recent insights into the complex molecular mechanisms regulating food intake. The aims were to emphasize on the interaction between central and peripheral actions of some of the key players acting not only at the hypothalamic level but also at the periphery. Presentations were focused on melanocortin-3 receptor (MC3R) and melanin-concentrating hormone (MCH) as anorexigenic and orexigenic components of the hypothalamus, on endocannabinoid receptors, initially as a central neuromodulatory signal, and on glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as peripheral signals. What becomes clear from these four presentations is that the regulation of food intake and energy homeostasis involves several overlapping pathways, and that we have only touched the tip of the iceberg. From the examples presented in this symposium, it could be expected that in the near future, in addition to a low-fat diet and exercise, a combination of appropriate peptides and small molecules is likely to become available to improve/facilitate the objectives of long-term maintenance of energy balance and body weight.

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“…More consistently, however, Mc3r −/− mice show greater feeding efficiency (the ratio of weight gain to energy intake) [36]. They have also been reported to have decreased locomotor activity particularly during the dark phase [41] and altered circadian rhythmicity in constant dark conditions [42]. They are, under most conditions hypophagic or normophagic relative to controls and appear to maintain normal metabolic rate and metabolic profiles despite their obese phenotype.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity

Demidowich¹,

Jun²,

Yanovski³

2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Inactivating mutations in the melanocortin 3 receptor (Mc3r) have been described as causing obesity in mice, but the physiologic effects of MC3R mutations in humans have been less clear. Here we review the MC3R polymorphisms and mutations identified in humans, and the in vitro, murine, and human cohort studies examining their putative effects. Some, but not all, studies suggest that the common human MC3R variant T6K+V81I, as well as several other rare, function-altering mutations, are associated with greater adiposity and hyperleptinemia with altered energy partitioning. In vitro, the T6K+V81I variant appears to decrease MC3R expression and therefore cAMP generation in response to ligand binding. Knockin mouse studies confirm the T6K+V81I variant increases feeding efficiency and the avidity with which adipocytes derived from bone or adipose tissue stem cells store triglycerides. Other MC3R mutations occur too infrequently in the human population to make definitive conclusions regarding their clinical effects.

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The role of melanocortin neuronal pathways in circadian biology: a new homeostatic output involving melanocortin‐3 receptors?

Cited by 18 publications

References 116 publications

Melanocortin-3 receptor regulates the normal fasting response

Melanocortin-3 receptor regulates the normal fasting response

Central (mainly) actions of GPCRs in energy homeostasis/balance: view from the Chair

Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity

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