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Melanocortin system

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https://www.readbyqxmd.com/read/28333235/ovarian-hormones-and-obesity
#1
Brigitte Leeners, Nori Geary, Philippe N Tobler, Lori Asarian
BACKGROUND: Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. OBJECTIVE AND RATIONALE: We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE...
March 2, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28323039/pomc-and-npy-mrna-expression-during-development-is-increased-in-rat-offspring-brain-from-mothers-fed-with-a-high-fat-diet
#2
Marianne Orlandini Klein, Harry MacKay, Alexander Edwards, Su-Bin Park, Ana Carolina Inhasz Kiss, Luciano Freitas Felicio, Alfonso Abizaid
Developmental programming is influenced by perinatal nutrition and it has long-lasting impacts on adult metabolism in the offspring. In particular, maternal high fat diet has been associated with increased risk of obesity and metabolic disorders during adulthood in the descendants. These effects may be due to the effects of the high fat diet on the development of the systems that regulate food intake and energy balance in the offspring hypothalamus. The arcuate nucleus (ARC) may be a particularly sensitive region to it as this nucleus contains the POMC and AgRP/NPY neurons that integrate the melanocortin system...
March 18, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28299639/age-related-changes-in-central-effects-of-corticotropin-releasing-factor-crf-suggest-a-role-for-this-mediator-in-aging-anorexia-and-cachexia
#3
Judit Tenk, Ildikó Rostás, Nóra Füredi, Alexandra Mikó, Margit Solymár, Szilvia Soós, Balázs Gaszner, Diana Feller, Miklós Székely, Erika Pétervári, Márta Balaskó
Hypothalamic corticotropin-releasing factor (CRF) lays downstream to catabolic melanocortins and at least partly mediates their catabolic effects. Age-related changes in the melanocortin system (weak responsiveness in middle-aged and a strong one in old rats) have been shown to contribute to middle-aged obesity and later to aging anorexia and cachexia of old age groups. We hypothesized that catabolic (anorexigenic and hypermetabolic) CRF effects vary with aging similarly to those of melanocortins. Thus, we aimed to test whether age-related variations of CRF effects may also contribute to middle-aged obesity and aging anorexia leading to weight loss of old age groups...
February 2017: Geroscience
https://www.readbyqxmd.com/read/28274841/role-of-the-brain-melanocortins-in-blood-pressure-regulation
#4
Jussara M do Carmo, Alexandre A da Silva, Zhen Wang, Taolin Fang, Nicola Aberdein, Cecilia E Perez de Lara, John E Hall
Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals. In experimental models of hypertension with high SNS activity, blockade of the melanocortin-4 receptor (MC4R) reduces BP despite causing marked hyperphagia and obesity. Activation of the central nervous system (CNS) pro-opiomelanocortin (POMC)-MC4R pathway appears to be an important link between obesity, SNS activation and hypertension...
March 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28267582/melanocortin-4-receptor-ligands-modulate-energy-homeostasis-through-urocortin-1-neurons-of-the-centrally-projecting-edinger-westphal-nucleus
#5
Nóra Füredi, Ákos Nagy, Alexandra Mikó, Gergely Berta, Tamás Kozicz, Erika Pétervári, Márta Balaskó, Balázs Gaszner
The role of the urocortin 1 (Ucn1) expressing centrally projecting Edinger-Westphal (EWcp) nucleus in energy homeostasis and stress adaptation response has previously been investigated. Morphological and functional studies have proven that orexigenic and anorexigenic peptidergic afferents and receptors for endocrine messengers involved in the energy homeostasis are found in the EWcp. The central role of the hypothalamic melanocortin system in energy homeostasis is well known, however, no data have been published so far on possible crosstalk between melanocortins and EWcp-Ucn1...
March 3, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28264929/the-agouti-related-peptide-binds-heparan-sulfate-through-segments-critical-for-its-orexigenic-effects
#6
Rafael Palomino, Hsiau-Wei Lee, Glenn L Millhauser
Syndecans potently modulate agouti-related peptide (AgRP) signaling in the central melanocortin system. Through heparan sulfate moieties, syndecans are thought to anchor AgRP near its receptor, enhancing its orexigenic effects. Original work proposed that AgRP's N-terminal domain facilitates this interaction. However, this is not compatible with evidence that this domain is post-translationally cleaved. Addressing this long-standing incongruity, we used calorimetry and magnetic resonance to probe interactions of AgRP peptides with glycosaminoglycans including heparan sulfate...
March 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28243712/altered-sucrose-self-administration-following-injection-of-melanocortin-receptor-agonists-and-antagonists-into-the-ventral-tegmental-area
#7
Laranci Shanmugarajah, Anna I Dunigan, Kyle J Frantz, Aaron G Roseberry
RATIONALE AND OBJECTIVES: Alpha-melanocyte stimulating hormone (αMSH) and agouti-related protein (AgRP) are antagonistic neuropeptides that play an important role in the control of feeding and body weight through their central actions on the melanocortin-3 and melanocortin-4 receptors. Increasing evidence indicates that αMSH and AgRP can interact with the mesolimbic dopamine system to regulate feeding as well as other behaviors. For example, we have shown previously that injection of melanocortin receptor agonists and antagonists into the ventral tegmental area (VTA) alters both normal home-cage feeding and the intake of sucrose solutions, but it remains unknown whether αMSH and AgRP can also act in the VTA to affect reward-related feeding...
February 27, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28236139/iron-dopamine-genetics-and-hormones-in-the-pathophysiology-of-restless-legs-syndrome
#8
REVIEW
Farhan H Khan, Caitlyn D Ahlberg, Christopher A Chow, Divya R Shah, Brian B Koo
Restless legs syndrome (RLS) is a common, chronic neurologic condition, which causes a persistent urge to move the legs in the evening that interferes with sleep. Human and animal studies have been used to study the pathophysiologic state of RLS and much has been learned about the iron and dopamine systems in relation to RLS. Human neuropathologic and imaging studies have consistently shown decreased iron in different brain regions including substantia nigra and thalamus. These same areas also demonstrate a state of relative dopamine excess...
February 24, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28229938/participation-of-ghrelin-signalling-in-the-reciprocal-regulation-of-hypothalamic-npy-pomc-mediated-appetite-control-in-amphetamine-treated-rats
#9
Ching-Han Yu, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh, Dong-Yih Kuo
Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared...
February 14, 2017: Appetite
https://www.readbyqxmd.com/read/28220105/acth-receptor-mc2r-specificity-what-do-we-know-about-underlying-molecular-mechanisms
#10
REVIEW
Davids Fridmanis, Ance Roga, Janis Klovins
Coincidentally, the release of this Research Topic in Frontiers in Endocrinology takes place 25 years after the discovery of the adrenocorticotropic hormone receptor (ACTHR) by Mountjoy and colleagues. In subsequent years, following the discovery of other types of mammalian melanocortin receptors (MCRs), ACTHR also became known as melanocortin type 2 receptor (MC2R). At present, five types of MCRs have been reported, all of which share significant sequence similarity at the amino acid level, and all of which specifically bind melanocortins (MCs)-a group of biologically active peptides generated by proteolysis of the proopiomelanocortin precursor...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28192062/pomc-neurons-from-birth-to-death
#11
Chitoku Toda, Anna Santoro, Jung Dae Kim, Sabrina Diano
The hypothalamus is an evolutionarily conserved brain structure that regulates an organism's basic functions, such as homeostasis and reproduction. Several hypothalamic nuclei and neuronal circuits have been the focus of many studies seeking to understand their role in regulating these basic functions. Within the hypothalamic neuronal populations, the arcuate melanocortin system plays a major role in controlling homeostatic functions. The arcuate pro-opiomelanocortin (POMC) neurons in particular have been shown to be critical regulators of metabolism and reproduction because of their projections to several brain areas both in and outside of the hypothalamus, such as autonomic regions of the brain stem and spinal cord...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28164623/decreased-synovial-fluid-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh-levels-reflect-disease-severity-in-patients-with-posttraumatic-ankle-osteoarthritis
#12
Guangyu Liu, Yunzhen Chen, Guichun Wang, Jianbing Niu
BACKGROUND: α-Melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin peptide, has been demonstrated to have anti-inflammation effects and protect against cartilage damage. Objective In this study, we aimed to investigate whether α-MSH in ankle joint synovial fluid is associated with the disease severity of posttraumatic ankle osteoarthritis (PTAOA). METHODS: 66 PTAOA patients undergoing ankle arthroscopical debridement or ankle joint replacement were enrolled in the study...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28051332/activation-of-the-central-melanocortin-system-chronically-reduces-body-mass-without-the-necessity-of-long-term-caloric-restriction
#13
I Côté, Y Sakarya, N Kirichenko, D Morgan, C S Carter, N Tümer, P J Scarpace
Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6-7/group) over 40 days...
October 19, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28048872/we-fg-bra-10-radiodosimetry-of-a-novel-alpha-particle-therapy-targeted-to-uveal-melanoma-absorbed-dose-to-organs-in-mice
#14
Christopher J Tichacek, Narges K Tafreshi, Mikalai M Budzevich, Epifanio Ruiz, Thaddeus J Wadas, Mark L McLaughlin, Eduardo G Moros, David L Morse
PURPOSE: The melanocortin-1 receptor (MC1R) is expressed in 94% of uveal melanomas and is described as an ideal target for this untreatable disease. MC1RL is a high affinity MC1R specific peptidomimetic ligand that can serve as a scaffold for therapeutic conjugates such as alpha particle emitting isotopes. The purpose of this study was to assess normal tissue distribution and risk as a result of using the DOTA chelator conjugated to MC1RL to deliver (225) Ac: MC1RL-DOTA-(225) Ac. METHODS: 17 non-tumor bearing BALB/c mice were intravenously injected with the novel MC1RL-DOTA-(225) Ac radiopharmaceutical with an average initial administered activity of 2...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045525/a-macrocyclic-agouti-related-protein-nle-4-dphe-7-%C3%AE-melanocyte-stimulating-hormone-chimeric-scaffold-produces-subnanomolar-melanocortin-receptor-ligands
#15
Mark D Ericson, Katie T Freeman, Sathya M Schnell, Carrie Haskell-Luevano
The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4,DPhe7]α-melanocyte stimulating hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp replaced the Arg-Phe-Phe sequence in the AGRP active loop derivative c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was the native Asn of AGRP or a diaminopropionic (Dap) acid residue previously shown to increase antagonist potency at the mMC4R...
January 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28030540/severe-atherosclerosis-and-hypercholesterolemia-in-mice-lacking-both-the-melanocortin-type-4-receptor-and-low-density-lipoprotein-receptor
#16
Vera Lede, Christin Franke, Andrej Meusel, Daniel Teupser, Albert Ricken, Joachim Thiery, Jürgen Schiller, Daniel Huster, Torsten Schöneberg, Angela Schulz
Dysfunction of the melanocortin system can result in severe obesity accompanied with dyslipidemia and symptoms of the metabolic syndrome but the effect on vascular atherogenesis is not known. To study the impact of obesity and dyslipidemia on the cardiovascular system, we generated mice double-deficient for the melanocortin type 4 receptor (Mc4rmut mice) and the LDL receptor (Ldlr-/- mice). Mc4rmut mice develop obesity due to hyperphagia. Double-mutant mice (Mc4rmut;Ldlr-/-) exhibited massive increases in body weight, plasma cholesterol and triacylglycerol levels and developed atherosclerosis...
2016: PloS One
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#17
REVIEW
Adriaan W Bruijnzeel
RATIONALE: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking...
December 28, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/28019657/the-melanoma-linked-redhead-mc1r-influences-dopaminergic-neuron-survival
#18
Xiqun Chen, Hongxiang Chen, Waijiao Cai, Michael Maguire, Bailiu Ya, Fuxing Zuo, Robert Logan, Hui Li, Katey Robinson, Charles R Vanderburg, Yang Yu, Yinsheng Wang, David E Fisher, Michael A Schwarzschild
OBJECTIVE: Individuals with Parkinson disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo...
December 26, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/28013339/genetics-of-obesity-can-an-old-dog-teach-us-new-tricks
#19
REVIEW
Giles S H Yeo
At one level, obesity is clearly a problem of simple physics, a result of eating too much and not expending enough energy. The more complex question, however, is why do some people eat more than others? Studies of human and mouse genetics over the past two decades have uncovered a number of pathways within the brain that play a key role in the control of food intake. A prime example is the leptin-melanocortin pathway, which we now know greatly contributes to mammalian appetitive behaviour. However, genetic disruption of this pathway remains rare and does not represent the major burden of the disease that is carried by those of us with 'common obesity'...
December 24, 2016: Diabetologia
https://www.readbyqxmd.com/read/28009464/effect-of-melanotan-ii-on-brain-fos-immunoreactivity-and-oxytocin-neuronal-activity-and-secretion-in-rats
#20
L Paiva, N Sabatier, G Leng, M Ludwig
Melanocortins stimulate the central oxytocin systems that are involved in regulating social behaviours. Alterations in central oxytocin have been linked to neurological disorders such as autism, and melanocortins have been proposed for therapeutic treatment. In the present study, we investigated how systemic administration of melanotan-II (MT-II), a melanocortin agonist, affects oxytocin neuronal activity and secretion in rats. The results obtained show that i.v., but not intranasal, administration of MT-II markedly induced Fos expression in magnocellular neurones of the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, and this response was attenuated by prior i...
February 2017: Journal of Neuroendocrinology
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