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Melanocortin activity

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https://www.readbyqxmd.com/read/28323920/perinatal-exposure-to-low-dose-bisphenol-a-bpa-disrupts-the-structural-and-functional-development-of-the-hypothalamic-feeding-circuitry
#1
Harry MacKay, Zachary R Patterson, Alfonso Abizaid
Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor due to observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subject to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a pre-existing phenotype produced by BPA exposure...
February 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28303974/antifibrotic-effect-of-pirfenidone-in-a-mouse-model-of-human-nonalcoholic-steatohepatitis
#2
Chikara Komiya, Miyako Tanaka, Kyoichiro Tsuchiya, Noriko Shimazu, Kentaro Mori, Shunsaku Furuke, Yasutaka Miyachi, Kumiko Shiba, Shinobu Yamaguchi, Kenji Ikeda, Kozue Ochi, Kazuhiko Nakabayashi, Ken-Ichiro Hata, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis with lobular inflammation and hepatocyte injury. Pirfenidone (PFD) is an orally bioavailable pyridone derivative that has been clinically used for the treatment of idiopathic pulmonary fibrosis. However, it remains unknown whether PFD improves liver fibrosis in a mouse model with human NASH-like phenotypes. In this study, we employed melanocortin 4 receptor-deficient (MC4R-KO) mice as a mouse model with human NASH-like phenotypes to elucidate the effect and action mechanisms of PFD on the development of NASH...
March 17, 2017: Scientific Reports
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/28294152/melanocortin-3-receptors-expressed-in-nkx2-1-ve-neurons-are-sufficient-for-controlling-appetitive-responses-to-hypocaloric-conditioning
#4
Clémence Girardet, Maria M Mavrikaki, Joseph R Stevens, Courtney A Miller, Daniel L Marks, Andrew A Butler
Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is amplified with hypocaloric conditioning. C57BL/6J (B6) mice subjected to hypocaloric feeding schedules (HFS) exhibit compulsive behavioral responses involving food anticipatory activity (FAA) and caloric loading following food access. These homeostatic responses to calorie-poor environs are attenuated in B6 mice in which Mc3r transcription is suppressed by a lox-stop-lox sequence in the 5'UTR (Mc3r(TB/TB)). Here, we report that optimization of caloric loading in B6 mice subject to HFS, characterized by increased meal size and duration, is not observed in Mc3r(TB/TB) mice...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275132/impact-of-polyunsaturated-and-saturated-fat-overfeeding-on-the-dna-methylation-pattern-in-human-adipose-tissue-a-randomized-controlled-trial
#5
Alexander Perfilyev, Ingrid Dahlman, Linn Gillberg, Fredrik Rosqvist, David Iggman, Petr Volkov, Emma Nilsson, Ulf Risérus, Charlotte Ling
Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses.Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial.Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue...
March 8, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28274841/role-of-the-brain-melanocortins-in-blood-pressure-regulation
#6
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/28273060/mc4r-dependent-suppression-of-appetite-by-bone-derived-lipocalin-2
#7
Ioanna Mosialou, Steven Shikhel, Jian-Min Liu, Antonio Maurizi, Na Luo, Zhenyan He, Yiru Huang, Haihong Zong, Richard A Friedman, Jonathan Barasch, Patricia Lanzano, Liyong Deng, Rudolph L Leibel, Mishaela Rubin, Thomas Nicholas, Wendy Chung, Lori M Zeltser, Kevin W Williams, Jeffrey E Pessin, Stavroula Kousteni
Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28267582/melanocortin-4-receptor-ligands-modulate-energy-homeostasis-through-urocortin-1-neurons-of-the-centrally-projecting-edinger-westphal-nucleus
#8
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/28259754/mc1r-signaling-intracellular-partners-and-pathophysiological-implications
#9
REVIEW
Cecilia Herraiz, Jose C Garcia-Borron, Celia Jiménez-Cervantes, Conchi Olivares
The melanocortin-1 receptor (MC1R) preferentially expressed in melanocytes is best known as a key regulator of the synthesis of epidermal melanin pigments. Its paracrine stimulation by keratinocyte-derived melanocortins also activates DNA repair pathways and antioxidant defenses to build a complex, multifaceted photoprotective response. Many MC1R actions rely on cAMP-dependent activation of two transcription factors, MITF and PGC1α, but pleiotropic MC1R signaling also involves activation of mitogen-activated kinases and AKT...
March 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28242830/suppressed-sympathetic-outflow-to-skeletal-muscle-muscle-thermogenesis-and-activity-energy-expenditure-with-calorie-restriction
#10
Tariq I Almundarij, Chaitanya K Gavini, Colleen M Novak
During weight loss, adaptive thermogenesis occurs where energy expenditure (EE) is suppressed beyond that predicted for the smaller body size. Here, we investigated the contributions of resting and nonresting EE to the reduced total EE seen after 3 weeks of 50% calorie restriction (CR) in rats, focusing on activity-associated EE, muscle thermogenesis, and sympathetic outflow. Prolonged food restriction resulted in a 42% reduction in daily EE, through a 40% decrease in resting EE, and a 48% decline in nonresting EE These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28241436/gomisin-n-inhibits-melanogenesis-through-regulating-the-pi3k-akt-and-mapk-erk-signaling-pathways-in-melanocytes
#11
Jae Kyoung Chae, Lalita Subedi, Minsun Jeong, Yong Un Park, Chul Young Kim, Hakwon Kim, Sun Yeou Kim
Gomisin N, one of the lignan compounds found in Schisandra chinensis has been shown to possess anti-oxidative, anti-tumorigenic, and anti-inflammatory activities in various studies. Here we report, for the first time, the anti-melenogenic efficacy of Gomisin N in mammalian cells as well as in zebrafish embryos. Gomisin N significantly reduced the melanin content without cellular toxicity. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, Gomisin N downregulated the expression levels of key proteins that function in melanogenesis...
February 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28228747/from-bioinactive-acth-to-acth-antagonist-the-clinical-perspective
#12
REVIEW
Chiraz Ghaddhab, Jean-Marc Vuissoz, Johnny Deladoëy
The adrenocorticotropic hormone (ACTH) is a pituitary hormone derived from a larger peptide, the proopiomelanocortin (POMC), as are the MSHs (α-MSH, β-MSH, and γ-MSH) and the β-LPH-related polypeptides (Figure 1A). ACTH drives adrenal steroidogenesis and growth of the adrenal gland. ACTH is a 39 amino acid polypeptide that binds and activates its cognate receptor [melanocortin receptor 2 (MC2R)] through the two regions H6F7R8W9 and K15K16R17R18P19. Most POMC-derived polypeptides contain the H6F7R8W9 sequence that is conserved through evolution...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28220105/acth-receptor-mc2r-specificity-what-do-we-know-about-underlying-molecular-mechanisms
#13
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/28207798/altered-hepatic-lipid-metabolism-in-mice-lacking-both-the-melanocortin-type-4-receptor-and-low-density-lipoprotein-receptor
#14
Vera Lede, Andrej Meusel, Antje Garten, Yulia Popkova, Melanie Penke, Christin Franke, Albert Ricken, Angela Schulz, Wieland Kiess, Daniel Huster, Torsten Schöneberg, Jürgen Schiller
Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4rmut) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism...
2017: PloS One
https://www.readbyqxmd.com/read/28152402/molecular-cloning-tissue-distribution-and-pharmacological-characterization-of-melanocortin-4-receptor-in-grass-carp-ctenopharyngodon-idella
#15
L Li, Z Yang, Y-P Zhang, S He, X-F Liang, Y-X Tao
Melanocortin-4 receptor (MC4R) plays a pivotal role in the mediation of leptin action on food intake and energy expenditure in mammals. The MC4R has also been identified in several teleosts, and its importance in the regulation of fish energy homeostasis is emerging. We herein reported on the molecular cloning, tissue distribution, and pharmacological characterization of MC4R in grass carp (Ctenopharyngodon idella), an economically and ecologically important fish. We showed that grass carp MC4R (ciMC4R) consisted of a 981 bp open reading frame encoding a protein of 326 amino acids, highly homologous (>95%) to several teleost MC4Rs...
November 21, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28150230/melanocortin-receptor-4-gene-polymorphisms-in-glioblastoma-patients-treated-with-concomitant-radio-chemotherapy
#16
Francesco Pasqualetti, Paola Orlandi, Vittorio Simeon, Martina Cantarella, Daniela Giuliani, Teresa Di Desidero, Alessandra Gonnelli, Durim Delishaj, Giuseppe Lombardi, Andrea Sechi, Marc Sanson, Vittorina Zagonel, Fabiola Paiar, Romano Danesi, Salvatore Guarini, Guido Bocci
Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled...
February 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28146118/jun-dimerization-protein-2-activates-mc2r-transcriptional-activity-role-of-phosphorylation-and-sumoylation
#17
Chiung-Min Wang, Raymond X Wang, Runhua Liu, Wei-Hsiung Yang
Jun dimerization protein 2 (JDP2), a basic leucine zipper transcription factor, is involved in numerous biological and cellular processes such as cancer development and regulation, cell-cycle regulation, skeletal muscle and osteoclast differentiation, progesterone receptor signaling, and antibacterial immunity. Though JDP2 is widely expressed in mammalian tissues, its function in gonads and adrenals (such as regulation of steroidogenesis and adrenal development) is largely unknown. Herein, we find that JDP2 mRNA and proteins are expressed in mouse adrenal gland tissues...
January 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28138237/preparation-cytotoxicity-and-in-vivo-antitumor-efficacy-of-111-in-labeled-modular-nanotransporters
#18
Tatiana A Slastnikova, Andrey A Rosenkranz, Natalia B Morozova, Maria S Vorontsova, Vasiliy M Petriev, Tatiana N Lupanova, Alexey V Ulasov, Michael R Zalutsky, Raisa I Yakubovskaya, Alexander S Sobolev
PURPOSE: Modular nanotransporters (MNTs) are a polyfunctional platform designed to achieve receptor-specific delivery of short-range therapeutics into the cell nucleus by receptor-mediated endocytosis, endosome escape, and targeted nuclear transport. This study evaluated the potential utility of the MNT platform in tandem with Auger electron emitting (111)In for cancer therapy. METHODS: Three MNTs developed to target either melanocortin receptor-1 (MC1R), folate receptor (FR), or epidermal growth factor receptor (EGFR) that are overexpressed on cancer cells were modified with p-SCN-Bn-NOTA and then labeled with (111)In in high specific activity...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28103316/alpha-melanocyte-stimulating-hormone-protects-against-cytokine-induced-barrier-damage-in-caco-2-intestinal-epithelial-monolayers
#19
Judit Váradi, András Harazin, Ferenc Fenyvesi, Katalin Réti-Nagy, Péter Gogolák, György Vámosi, Ildikó Bácskay, Pálma Fehér, Zoltán Ujhelyi, Gábor Vasvári, Eszter Róka, David Haines, Mária A Deli, Miklós Vecsernyés
Alpha-melanocyte-stimulating hormone (α-MSH) is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER) and permeability for marker molecules...
2017: PloS One
https://www.readbyqxmd.com/read/28094871/divergence-of-camp-signaling-pathways-mediating-augmented-nucleotide-excision-repair-and-pigment-induction-in-melanocytes
#20
Erin M Wolf Horrell, Stuart G Jarrett, Katharine M Carter, John A D'Orazio
Loss-of-function melanocortin 1 receptor (MC1R) polymorphisms are common in UV-sensitive fair-skinned individuals and are associated with blunted cAMP second messenger signaling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signaling positions melanocytes to resist UV injury by up-regulating synthesis of UV-blocking eumelanin pigment and by enhancing the repair of UV-induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP-activated protein kinase (protein kinase A)-mediated phosphorylation of the ataxia telangiectasia mutated and Rad3 related (ATR) protein on the S435 residue...
January 17, 2017: Experimental Dermatology
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