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Melanocortin system

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https://www.readbyqxmd.com/read/29031726/reduced-renal-sympathetic-nerve-activity-contributes-to-elevated-glycosuria-and-improved-glucose-tolerance-in-hypothalamus-specific-pomc-knockout-mice
#1
Kavaljit H Chhabra, Donald A Morgan, Benjamin P Tooke, Jessica M Adams, Kamal Rahmouni, Malcolm J Low
OBJECTIVE: Hypothalamic arcuate nucleus-specific pro-opiomelanocortin deficient (ArcPomc(-/-)) mice exhibit improved glucose tolerance despite massive obesity and insulin resistance. We demonstrated previously that their improved glucose tolerance is due to elevated glycosuria. However, the underlying mechanisms that link glucose reabsorption in the kidney with ArcPomc remain unclear. Given the function of the hypothalamic melanocortin system in controlling sympathetic outflow, we hypothesized that reduced renal sympathetic nerve activity (RSNA) in ArcPomc(-/-) mice could explain their elevated glycosuria and consequent enhanced glucose tolerance...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031713/peripheral-cannabinoid-1-receptor-blockade-restores-hypothalamic-leptin-signaling
#2
Joseph Tam, Gergő Szanda, Adi Drori, Ziyi Liu, Resat Cinar, Yoshihiro Kashiwaya, Marc L Reitman, George Kunos
OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB1R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB1R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031712/mitochondrial-uncoupling-in-the-melanocortin-system-differentially-regulates-npy-and-pomc-neurons-to-promote-weight-loss
#3
Natalie Jane Michael, Stephanie Elise Simonds, Marco van den Top, Michael Alexander Cowley, David Spanswick
OBJECTIVE: The mitochondrial uncoupling agent 2,4-dinitrophenol (DNP), historically used as a treatment for obesity, is known to cross the blood-brain-barrier, but its effects on central neural circuits controlling body weight are largely unknown. As hypothalamic melanocortin neuropeptide Y/agouti-related protein (NPY/AgRP) and pro-opiomelanocortin (POMC) neurons represent key central regulators of food intake and energy expenditure we investigated the effects of DNP on these neurons, food intake and energy expenditure...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030576/genetic-induction-of-hypometabolism-by-ablation-of-mc4r-does-not-suppress-als-like-phenotypes-in-the-g93a-mutant-sod1-mouse-model
#4
Shachee Doshi, Preetika Gupta, Robert G Kalb
Dysfunction and death of motor neurons leads to progressive paralysis in amyotrophic lateral sclerosis (ALS). Recent studies have reported organism-level metabolic dysfunction as a prominent but poorly understood feature of the disease. ALS patients are hypermetabolic with increased resting energy expenditure, but if and how hypermetabolism contributes to disease pathology is unknown. We asked if decreasing metabolism in the mutant superoxide dismutase 1 (SOD1) mouse model of ALS (G93A SOD1) would alter motor function and survival...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28975585/polymorphisms-in-genes-involved-in-the-leptin-melanocortin-pathway-are-associated-with-obesity-related-cardiometabolic-alterations-in-a-southern-chilean-population
#5
Victor Manriquez, Jorge Aviles, Luis Salazar, Nicolas Saavedra, Pamela Seron, Fernando Lanas, Cristina Moreno Fajardo, Mario Hiroyuki Hirata, Rosario Dominguez Crespo Hirata, Alvaro Cerda
BACKGROUND: Polymorphisms in genes encoding proteins of the leptin-melanocortin pathway have been associated with obesity. The involvement of these polymorphisms with changes in body mass index (BMI) and anthropometric measures could also imply a contribution to the risk of metabolic syndrome (MetS) and metabolic alterations. We evaluated the relationship of leptin-melanocortin system polymorphisms with obesity, MetS, and other metabolic alterations in Southern Chilean individuals. METHODS: Two-hundred individuals were grouped as normoweight (BMI 18...
October 3, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28947386/human-melanocortin-1-receptor-mediated-ubiquitination-of-nonvisual-arrestins-role-of-mahogunin-ring-finger-1-e3-ligase
#6
Marta Abrisqueta, Concepción Olivares, Cecilia Herraiz, María Castejón-Griñán, Julia Sirés-Campos, José C García-Borrón, Celia Jiménez-Cervantes
Signaling from the melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor (GPCR) crucial for melanocyte proliferation and differentiation, is regulated by cytosolic β-arrestins (ARRBs). MC1R signaling is also negatively modulated by the E3-ubiquitin ligase Mahogunin Ring Finger-1 (MGRN1), whose mutation causes hyperpigmentation, congenital heart defects and neurodegeneration in mice. We showed previously that although MC1R interacts stably with human ARRB1 or ARRB2, only ARRB2 mediates receptor desensitization and internalization...
September 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28936166/nucleus-accumbens-mc4-r-stimulation-reduces-food-and-ethanol-intake-in-adult-rats-regardless-of-binge-like-ethanol-exposure-during-adolescence
#7
Francisca Carvajal, José M Lerma-Cabrera, Manuel Alcaraz-Iborra, Montserrat Navarro, Todd E Thiele, Inmaculada Cubero
The melanocortin (MC) system regulates feeding and ethanol consumption. Recent evidence shows that melanocortin 4 receptor (MC4-R) stimulation within the nucleus accumbens (NAc) elicits anorectic responses and reduces ethanol consumption and ethanol palatability in adult rats. Ethanol exposure during adolescence causes long-lasting changes in neural pathways critically involved in neurobehavioral responses to ethanol. In this regard, binge-like ethanol exposure during adolescence reduces basal alpha-melanocyte-stimulating hormone (α-MSH) and alters the levels of agouti-related peptide (AgRP) in hypothalamic and limbic areas...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28930194/developmental-programming-of-obesity-and-liver-metabolism-by-maternal-perinatal-nutrition-involves-the-melanocortin-system
#8
Paul Cordero, Jiawei Li, Vi Nguyen, Joaquim Pombo, Nuria Maicas, Marco Novelli, Paul D Taylor, Anne-Maj Samuelsson, Manlio Vinciguerra, Jude A Oben
Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO)...
September 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28915638/oleoylethanolamide-inhibits-%C3%AE-melanocyte-stimulating-hormone-stimulated-melanogenesis-via-erk-akt-and-creb-signaling-pathways-in-b16-melanoma-cells
#9
Juan Zhou, Tong Ren, Ying Li, Anran Cheng, Wanyi Xie, Lanxi Xu, Lu Peng, Jinbin Lin, Lianxiang Lian, Yong Diao, Xin Jin, Lichao Yang
The present study aimed to examine the potential inhibitory activity of oleoylethanolamide (OEA) on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis and the molecular mechanism(s) involved in the process in B16 mouse melanoma cells. Our data demonstrated that OEA markedly inhibited melanin synthesis and tyrosinase activity in α-MSH-stimulated B16 cells. In addition, the expression of melanogenesis-related proteins, such as melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase, was suppressed in a concentration-dependent manner by OEA...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28851749/the-thermogenic-effect-of-nesfatin-1-requires-recruitment-of-the-melanocortin-system
#10
Riccardo Dore, Luka Levata, Sogol Gachkar, Olaf Jöhren, Jens Mittag, Hendrik Lehnert, Carla Schulz
Nesfatin-1 is a bioactive polypeptide expressed both in the brain and peripheral tissues and involved in the control of energy balance by reducing food intake. Central administration of nesfatin-1 significantly increases energy expenditure, as demonstrated by a higher dry heat loss; yet, the mechanisms underlying the thermogenic effect of central nesfatin-1 remain unknown. Therefore, in this study, we sought to investigate whether the increase in energy expenditure induced by nesfatin-1 is mediated by the central melanocortin pathway, which was previously reported to mediate central nesfatin-1´s effects on feeding and numerous other physiological functions...
November 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28837761/diversification-and-convergence-of-aposematic-phenotypes-truncated-receptors-and-cellular-arrangements-mediate-rapid-evolution-of-coloration-in-harlequin-poison-frogs
#11
A Posso-Terranova, J A Andres
Aposematic signals represent one of the classical systems to study evolution and, as such, they have received considerable empirical and theoretical investigation. Despite the extensive literature on aposematic coloration, much uncertainty remains about genetic changes responsible for the repeated evolution of similar signals in multiple lineages. Here, we study the diversification and convergence of coloration among lineages of aposematic harlequin poison frogs (O. histrionica complex). Our results suggest that different background phenotypes, showing different color and/or luminance contrast, have evolved independently at least twice in this group...
August 24, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28813605/structure-activity-relationship-studies-on-a-macrocyclic-agouti-related-protein-agrp-scaffold-reveal-agouti-signaling-protein-asp-residue-substitutions-maintain-melanocortin-4-receptor-antagonist-potency-and-result-in-inverse-agonist-pharmacology-at-the-melanocortin
#12
Mark D Ericson, Katie T Freeman, Sathya M Schnell, Katlyn A Fleming, Carrie Haskell-Luevano
The melanocortin system consists of five reported receptors, agonists from the proopiomelanocortin gene transcript, and two antagonists, agouti-signaling protein (ASP) and agouti-related protein (AGRP). For both ASP and AGRP, the hypothesized Arg-Phe-Phe pharmacophores are on exposed β-hairpin loops. In this study, the Asn and Ala positions of a reported AGRP macrocyclic scaffold (c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro]) were explored with 14-compound and 8-compound libraries, respectively, to generate more potent, selective melanocortin receptor antagonists...
October 4, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28812266/oxytocin-and-social-relationships-from-attachment-to-bond-disruption
#13
Oliver J Bosch, Larry J Young
Social relationships throughout life are vital for well-being and physical and mental health. A significant amount of research in animal models as well as in humans suggests that oxytocin (OT) plays an important role in the development of the capacity to form social bonds, the mediation of the positive aspects of early-life nurturing on adult bonding capacity, and the maintenance of social bonding. Here, we focus on the extensive research on a socially monogamous rodent model organism, the prairie vole (Microtus ochrogaster)...
August 16, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28805746/melanocortins-melanocortin-receptors-and-multiple-sclerosis
#14
REVIEW
Robert P Lisak, Joyce A Benjamins
The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair...
August 14, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28775376/altered-circadian-feeding-behavior-and-improvement-of-metabolic-syndrome-in-obese-tac1-deficient-mice
#15
C A Maguire, S León, R S Carroll, U B Kaiser, V M Navarro
BACKGROUND: Metabolic function is regulated by the interplay of central and peripheral factors that ultimately regulate food intake and energy expenditure. The tachykinin substance P (SP) has been identified as a novel regulator of energy balance, however, the mechanisms underlying this effect are ill-defined and conflicting data regarding the role of SP on food intake have been reported by different groups. OBJECTIVE: To further characterize the metabolic role of the Tac1 gene products (SP and neurokinin A (NKA)) in mice through a series of genetic, metabolic and behavioral studies in Tac1 deficient mice...
August 4, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28739551/the-description-of-a-new-case-with-proopiomelanocortin-pomc-deficiency-an-increasingly-important-diagnosis-to-make
#16
Semra Çetinkaya, Tülay Güran, Erdal Kurnaz, Melikşah Keskin, Elif Sağsak, Senay Savaş Erdeve, Jenifer P Suntharalingham, Federica Buonocore, John Achermann, Zehra Aycan
International surveillance data suggests a worldwide epidemic of pediatric obesity regardless of geographic, socioeconomic, racial and ethnic factors. Reversing this epidemic of pediatric obesity will require recognition and understanding of the pathophysiology of the condition to enable us to develop novel therapies as well as taking measures to shift social attitudes and public policies at a global level. Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder of early-onset obesity, which has increased our insight into the important role of the leptin-melanocortin pathway in energy balance...
July 24, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28699792/novel-approaches-to-the-design-of-bioavailable-melanotropins
#17
REVIEW
Yang Zhou, Minying Cai
The melanocortin system is a primordial and critical system for survival, involved in a wide variety of physiological functions. It includes melanocortin receptors (MCRs) and melanotropin ligands (MCLs). MCRs are important drug targets that can regulate several key physiological processes. Extensive efforts have been made to develop peptide and peptidomimetics targeting melanocortin receptors including MC1R, MC3R, MC4R and MC5R. Most research is focused on developing potent and selective melanotropins. However, developing bioavailable melanotropins remains challenging...
October 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28690493/emerging-signaling-pathway-in-arcuate-feeding-related-neurons-role-of-the-acbd7
#18
REVIEW
Damien Lanfray, Denis Richard
The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28660550/clinical-and-economic-evaluation-of-repository-corticotropin-injection-a-narrative-literature-review-of-treatment-efficacy-and-healthcare-resource-utilization-for-seven-key-indications
#19
REVIEW
Michael Philbin, John Niewoehner, George J Wan
INTRODUCTION: Repository corticotropin injection (RCI; H.P. Acthar(®) Gel; Mallinckrodt Pharmaceuticals Inc., Hampton, NJ) is a highly purified, prolonged-release porcine preparation of adrenocorticotropic hormone (ACTH) analogue that is FDA-approved for treatment of 19 autoimmune and inflammatory disorders. The diverse physiological actions of RCI at the melanocortin receptors (MCRs) affect processes involved in inflammation, pigmentation, steroidogenesis, and immunomodulation. Although RCI has been approved to treat inflammatory and autoimmune diseases for more than 60 years, recent progress in understanding both MCRs and the effects of RCI in modulating immune responses has led to increased interest in RCI as a therapeutic choice...
June 28, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28627277/anti-acne-drugs-in-phase-1-and-2-clinical-trials
#20
REVIEW
Christos C Zouboulis, Clio Dessinioti, Fragkiski Tsatsou, Harald P M Gollnick
Despite the impressive increase of knowledge on acne etiology accumulated during the last 20 years, few efforts have been overtaken to introduce new therapeutic regiments targeting the ideal treatment of acne. The increasing emergence of microbial resistance associated with antibiotics, teratogenicity, particularly associated with systemic isotretinoin, and the need for an adverse drug profile, which can be tolerated by the patient, make the need of new pathogenesis relevant anti-acne agents an emerging issue...
July 2017: Expert Opinion on Investigational Drugs
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