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Melanocortin activity

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https://www.readbyqxmd.com/read/29329999/understanding-melanocortin-4-receptor-control-of-neuronal-circuits-toward-novel-therapeutics-for-obesity-syndrome
#1
REVIEW
Sang Hyeon Ju, Gyu-Bon Cho, Jong-Woo Sohn
It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin pathways regulate food intake, energy expenditure, and glucose homeostasis. Importantly, MC4R deficiency is the most common monogenic cause of human obesity. Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the different physiological function of MC4R stimulation. In addition, MC4Rs activate multiple intracellular and/or synaptic signaling molecules for the regulation of neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are plausible targets for development of novel therapeutics against obesity and obesity-related metabolic disorders...
January 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29317531/melanocortin-overexpression-limits-diet-induced-inflammation-and-atherosclerosis-in-ldlr-mice
#2
Salla Nuutinen, Liisa Ailanen, Eriika Savontaus, Petteri Rinne
Atherosclerosis is a chronic inflammatory disease of the arteries. The disease is initiated by endothelial dysfunction that allows the transport of leukocytes and low-density lipoprotein into the vessel wall forming atherosclerotic plaques. The melanocortin system is an endogenous peptide system that regulates, for example, energy homeostasis and cardiovascular function. Melanocortin treatment with endogenous or synthetic melanocortin peptides reduces body weight, protects the endothelium and alleviates vascular inflammation, but the long-term effects of melanocortin system activation on atheroprogression remain largely unknown...
January 9, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29315078/associations-between-the-components-of-metabolic-syndrome-and-the-polymorphisms-in-the-peroxisome-proliferator-activated-receptor-gamma-ppar-%C3%AE-the-fat-mass-and-obesity-associated-fto-and-the-melanocortin-4-receptor-mc4r-genes
#3
Małgorzata Szkup, Aleksander Jerzy Owczarek, Daria Schneider-Matyka, Jacek Brodowski, Beata Łój, Elżbieta Grochans
INTRODUCTION: Metabolic syndrome (MetS) is regarded as a set of abnormalities, increasing the risk of serious functioning disorders. It can develop as a result of genetic predisposition. AIM: The aim of this study was to establish associations between MetS-related abnormalities and the PPAR-γ rs1801282, FTO rs9939609, and MC4R rs17782313 polymorphisms. MATERIAL AND METHODS: The study involved 425 women aged 45-60 years. The participants were surveyed and subjected to anthropometric, biochemical and genetic analysis...
January 9, 2018: Aging
https://www.readbyqxmd.com/read/29297124/metabolic-parameters-and-functional-state-of-hypothalamic-signaling-systems-in-ay-a-mice-with-genetic-predisposition-to-obesity-and-the-effect-of-metformin
#4
K V Derkach, I O Zakharova, I V Romanova, I I Zorina, A L Mikhrina, A O Shpakov
The metabolic parameters and functional state of hypothalamic systems in mice with the Yellow mutation in the Agouti locus and with obesity of the melanocortin type and the effect of metformin (MF) treatment (9 days, 200 mg/kg/day) were studied. The MF treatment led to decreased body weight and to normalization of glucose tolerance in mice. In the hypothalamus, MF restored the decreased activity of Akt kinase, the main component of leptin pathway, and normalized the increased expression of subtype 1B serotonin receptor...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29290621/a-gut-brain-axis-regulating-glucose-metabolism-mediated-by-bile-acids-and-competitive-fibroblast-growth-factor-actions-at-the-hypothalamus
#5
Shunmei Liu, Genevieve Marcelin, Clemence Blouet, Jae Hoon Jeong, Young-Hwan Jo, Gary J Schwartz, Streamson Chua
OBJECTIVE: Bile acids have been implicated as important regulators of glucose metabolism via activation of FXR and GPBAR1. We have previously shown that FGF19 can modulate glucose handling by suppressing the activity of hypothalamic AGRP/NPY neurons. As bile acids stimulate the release of FGF19/FGF15 into the circulation, we pursued the potential of bile acids to improve glucose tolerance via a gut-brain axis involving FXR and FGF15/FGF19 within enterocytes and FGF receptors on hypothalamic AGRP/NPY neurons...
December 9, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29275211/up-regulation-of-pomc-and-cart-mrnas-by-intermittent-hypoxia-via-gata-transcription-factors-in-human-neuronal-cells
#6
Ryogo Shobatake, Ken Takasawa, Hiroyo Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Tomoko Uchiyama, Mai Makino, Kazuma Sugie, Shin Takasawa, Satoshi Ueno
Sleep apnea syndrome (SAS) is characterized by intermittent hypoxia (IH) during sleep. SAS and obesity are strongly related to each other. Here, we investigated the effect of IH on the expression of major appetite regulatory genes in human neuronal cells. We exposed NB-1, SH-SY5Y, and SK-N-SH human neuronal cells to IH (64 cycles of 5 min hypoxia and 10 min normoxia), normoxia, or sustained hypoxia for 24 h and measured the mRNA levels of proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), galanin, galanin-like peptide, ghrelin, pyroglutamylated RFamide peptide, agouti-related peptide, neuropeptide Y, and melanocortin 4 receptor by real-time RT-PCR...
December 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29247679/anti-leptin-receptor-antibodies-strengthen-leptin-biofunction-in-growing-chickens
#7
M M Lei, C K Wei, Z Chen, S Yosefi, H X Zhu, Z D Shi
Antibodies against the extracellular domains of the chicken leptin receptor were used to study the biological function of leptin in growing chickens. Both polyclonal and monoclonal antibodies were administered intramuscularly to 30-d-old Chinese indigenous Gushi pullets. Both antibody preparations increased feed intake for 6 h after injection and reduced plasma concentrations of glucose, triglycerides, and both high- and low-density lipoproteins. The antibody treatments also upregulated agouti-related peptide and neuropeptide Y in the hypothalamus and downregulated proopiomelanocortin, melanocortin 4 receptor, and leptin receptor...
December 13, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29226825/desacetyl-%C3%AE-melanocyte-stimulating-hormone-and-%C3%AE-melanocyte-stimulating-hormone-are-required-to-regulate-energy-balance
#8
Kathleen G Mountjoy, Alexandre Caron, Kristina Hubbard, Avik Shome, Angus C Grey, Bo Sun, Sarah Bould, Martin Middleditch, Beau Pontré, Ailsa McGregor, Paul W R Harris, Renata Kowalczyk, Margaret A Brimble, Rikus Botha, Karen M L Tan, Sarah J Piper, Christina Buchanan, Syann Lee, Anthony P Coll, Joel K Elmquist
OBJECTIVE: Regulation of energy balance depends on pro-opiomelanocortin (POMC)-derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating hormone (α-MSH) is the predicted natural POMC-derived peptide that regulates energy balance. Desacetyl-α-MSH, the precursor for α-MSH, is present in brain and blood. Desacetyl-α-MSH is considered to be unimportant for regulating energy balance despite being more potent (compared with α-MSH) at activating the appetite-regulating MC4R in vitro...
November 24, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29217655/regulation-of-lipolytic-response-and-energy-balance-by-melanocortin-2-receptor-accessory-protein-mrap-in-adipocytes
#9
Xiaodong Zhang, Alicia M Saarinen, Latoya E Campbell, Elena A De Filippis, Jun Liu
MRAP is highly expressed in adrenal gland and adipose tissue. In adrenal cells, MRAP is essential for ACTH-induced activation of the cAMP/PKA pathway by melanocortin 2 receptor (MC2R), leading to glucocorticoid production and secretion. Although ACTH was known to stimulate PKA-dependent lipolysis, the functional involvement of MRAP in adipocyte metabolism remains incompletely defined. Herein, we found that knockdown or overexpression of MRAP in 3T3-L1 adipocytes reduced or increased ACTH-induced lipolysis, respectively...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29215157/knockdown-of-the-transcript-of-extracellular-signal-regulated-kinase-in-the-brain-modulated-hypothalamic-neuropeptide-mediated-appetite-control-in-amphetamine-treated-rats
#10
Ching-Han Yu, Yih-Shou Hsieh, Pei-Ni Chen, Jeng-Rung Chen, Dong-Yih Kuo
BACKGROUND AND PURPOSE: Amphetamine (AMPH) is a releaser of dopamine stored in synaptic terminals, which can suppress appetite by changing the expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the hypothalamus. This study explored whether extracellular signal-regulated kinases (ERKs) were involved in appetite control mediated by cAMP response element binding protein (CREB), NPY and POMC in AMPH-treated rats. EXPERIMENTAL APPROACH: Rats were given AMPH for four days and changes in feeding behavior and expression levels of pERK, pCREB, NPY and melanocortin receptor 3 (MC3R) were examined and compared...
December 7, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29206201/selection-on-the-major-color-gene-melanocortin-1-receptor-shaped-the-evolution-of-the-melanocortin-system-genes
#11
Linda Dib, Luis M San-Jose, Anne-Lyse Ducrest, Nicolas Salamin, Alexandre Roulin
Modular genetic systems and networks have complex evolutionary histories shaped by selection acting on single genes as well as on their integrated function within the network. However, uncovering molecular coevolution requires the detection of coevolving sites in sequences. Detailed knowledge of the functions of each gene in the system is also necessary to identify the selective agents driving coevolution. Using recently developed computational tools, we investigated the effect of positive selection on the coevolution of ten major genes in the melanocortin system, responsible for multiple physiological functions and human diseases...
December 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29198512/understanding-the-role-of-serotonin-in-female-hypoactive-sexual-desire-disorder-and-treatment-options
#12
REVIEW
Harry A Croft
BACKGROUND: The neurobiology of sexual response is driven in part by dopamine and serotonin-the former modulating excitatory pathways and the latter regulating inhibitory pathways. Neurobiological underpinnings of hypoactive sexual desire disorder (HSDD) are seemingly related to overactive serotonin activity that results in underactive dopamine activity. As such, pharmacologic agents that decrease serotonin, increase dopamine, or some combination thereof, have therapeutic potential for HSDD...
December 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29182660/interaction-between-tcf7l2-polymorphism-and-dietary-fat-intake-on-high-density-lipoprotein-cholesterol
#13
Dhanasekaran Bodhini, Szilvia Gaal, Israa Shatwan, Kandaswamy Ramya, Basma Ellahi, Shelini Surendran, Vasudevan Sudha, Mohan R Anjana, Viswanathan Mohan, Julie A Lovegrove, Venkatesan Radha, Karani Santhanakrishnan Vimaleswaran
Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity...
2017: PloS One
https://www.readbyqxmd.com/read/29182034/molecular-imaging-and-radionuclide-therapy-of-melanoma-targeting-the-melanocortin-1-receptor
#14
Chengcheng Zhang, Kuo-Shyan Lin, François Bénard
Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29179997/elevated-cyclic-amp-levels-promote-brafca-pten-mouse-melanoma-growth-but-pcreb-is-negatively-correlated-with-human-melanoma-progression
#15
Carlos I Rodríguez, Edgardo Castro-Pérez, B Jack Longley, Vijayasaradhi Setaluri
Melanocyte development and differentiation are regulated by cAMP, which is produced by the adenylate cyclase (AC) enzyme upon activation of the melanocortin-1-receptor (MC1R). Individuals carrying single amino acid substitution variants of MC1R have impaired cAMP signaling and higher risk of melanoma. However, the contribution of AC to this risk is not clear. Downstream of AC, the phosphorylated transcription factor, cyclic AMP Responsive Element Binding Protein (pCREB), which is activated by protein kinase A, regulates the expression of several genes including the melanocyte master regulator MITF...
November 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29131966/activation-of-the-central-melanocortin-system-in-rats-persistently-reduces-body-and-fat-mass-independently-of-caloric-reduction
#16
Isabelle Côté, Sara M Green, Drake Morgan, Christy Carter, Nihal Tümer, Philip James Scarpace
Recent evidence indicate that Melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to Melanotan II (MTII), we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison to a group of animals that were pair-fed (PF) to the MTII group...
November 13, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29124692/ultraviolet-radiations-skin-defense-damage-mechanism
#17
Dheeraj Mohania, Shikha Chandel, Parveen Kumar, Vivek Verma, Kumar Digvijay, Deepika Tripathi, Khushboo Choudhury, Sandeep Kumar Mitten, Dilip Shah
UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29113896/neuroinflammation-produced-by-heavy-alcohol-intake-is-due-to-loops-of-interactions-between-toll-like-4-and-tnf-receptors-peroxisome-proliferator-activated-receptors-and-the-central-melanocortin-system-a-novel-hypothesis-and-new-therapeutic-avenues
#18
Osvaldo Flores-Bastías, Eduardo Karahanian
Excessive alcohol intake induces an inflammatory response in the brain, via TNFα, TLR4 and NF-κB signaling pathways. It has been proposed that neuroinflammation would play a very important role in the development of alcohol addiction. In addition to stimulating the synthesis of inflammatory mediators such as IL-6, IL-1β and TNFα, NF-κB is capable of reducing the anti-inflammatory activity of PPARα and PPARγ. Reciprocally, PPARα, PPARγ and melanocortin 4 receptor (MC4R) can decrease the proinflammatory activity of NF-κB, establishing an interplay of inactivations between such nuclear factors and receptors...
November 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29099963/activity-of-the-hypothalamic-melanocortin-system-decreases-in-middle-aged-and-increases-in-old-rats
#19
Nóra Füredi, Alexandra Mikó, Balázs Gaszner, Diána Feller, Ildikó Rostás, Judit Tenk, Margit Solymár, Márta Balaskó, Erika Pétervári
Appearance of middle-aged obesity and aging anorexia both in humans and rodents suggests a role for regulatory alterations. Hypothalamic melanocortin agonist, alpha-melanocyte-stimulating hormone (alpha-MSH) produced in the arcuate nucleus (ARC) reduces body weight via inducing hypermetabolism and anorexia mainly through melanocortin 4 receptors (MC4R) in the paraventricular nucleus (PVN). Orexigenic ARC-derived agouti-related protein (AgRP) is an inverse agonist on MC4R in the PVN. Previously we demonstrated that characteristic age-related shifts in the catabolic effects of alpha-MSH may contribute both to middle-aged obesity and aging anorexia...
November 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29097517/neuropeptides-in-obesity-and-metabolic-disease
#20
REVIEW
Agatha A van der Klaauw
BACKGROUND: The global rise in the prevalence of obesity and associated comorbidities such as type 2 diabetes, cardiovascular disease, and cancer represents a major public health concern. CONTENT: Studies in rodents with the use of global and targeted gene disruption, and mapping of neurocircuitry by using optogenetics and designer receptors exclusively activated by designer drugs (DREADDs) have greatly advanced our understanding of the neural control of body weight...
November 2, 2017: Clinical Chemistry
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