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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
Luis Paiva, Nancy Sabatier, Gareth Leng, Mike Ludwig
Melanocortins stimulate the central oxytocin systems which 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. Here, we investigated how systemic administration of melanotan-II (MT-II), a melanocortin agonist, affects oxytocin neuronal activity and secretion in rats. Our results show that intravenous (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 intracerebroventricular (i...
December 23, 2016: Journal of Neuroendocrinology
Jing Cui, Yi Ding, Shu Chen, Xiaoqiang Zhu, Yichen Wu, Mingliang Zhang, Yaxin Zhao, Tong-Ruei R Li, Ling V Sun, Shimin Zhao, Yuan Zhuang, Weiping Jia, Lei Xue, Min Han, Tian Xu, Xiaohui Wu
A rise in the occurrence of obesity has driven exploration of its underlying genetic basis and potential targets for intervention. GWAS studies have identified obesity susceptibility pathways involving several neuropeptides that control energy homeostasis, suggesting that variations in the genes that regulate food intake and energy expenditure may contribute to obesity. In this study, we identified 5 additional obesity loci, including a neuronal orphan GPCR called Gpr45, in a forward genetic screen of mutant mice generated by piggyBac insertional mutagenesis...
September 1, 2016: Journal of Clinical Investigation
Chaitanya K Gavini, William C Jones, Colleen M Novak
KEY POINTS: The ventromedial hypothalamus (VMH) and the central melanocortin system both play vital roles in regulating energy balance by modulating energy intake and utilization. Recent evidence suggests that activation of the VMH alters skeletal muscle metabolism. We show that intra-VMH melanocortin receptor activation increases energy expenditure and physical activity, switches fuel utilization to fats, and lowers work efficiency such that excess calories are dissipated by skeletal muscle as heat...
September 15, 2016: Journal of Physiology
N M Bazhan, E V Kulikova, E N Makarova, T V Yakovleva, A Yu Kazantseva
Melanocortin (MC) system regulates food intake under the rest conditions. Stress inhibits food intake. It is not clear whether brain MC system is involved in stress-induced anorexia in mice. The aim of the work was to investigate the effect of pharmacological blockade and activation of brain MC receptors on food intake under stress. C57B1/6J male mice were subjected to ether stress (0.5 minute ether anesthesia) before the administration of saline solution or synthetic non-selective blocker (SHU9119) or agonist (Melanotan II) of MC receptors into the lateral brain ventricle...
December 2015: Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova
Rebekah Brennan, John S G Wells, Marie Claire Van Hout
Injecting use of image and performance-enhancing drugs (IPED) in the general population is a public health concern. A wide and varied range of IPED are now easily accessible to all through the online market. A comprehensive literature review was undertaken according to Critical Appraisal Skills Programme (CASP) guidelines for systematic review, to identify the relevant literature. No date restrictions were placed on the database search in the case of human growth hormone melanotan I and II, and oil and cosmetic injectables...
January 25, 2016: Health & Social Care in the Community
Kavaljit H Chhabra, Jessica M Adams, Brian Fagel, Daniel D Lam, Nathan Qi, Marcelo Rubinstein, Malcolm J Low
Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance...
March 2016: Diabetes
Bastiaan J Venhuis, Peter H J Keizers, Rüdiger Klausmann, Ingrid Hegger
Operation Pangea is an annual international week of action combating pharmaceutical crime. In this study, called Operation Resistance, we asked the national agencies in Europe to search for falsified antibiotics and biopharmaceutical injectables (peptides and proteins) amongst the medicines seized in Pangea 7 (2014). Reports were received from Belgium, Cyprus, Czech Republic, Denmark, France, the Netherlands, Portugal, Sweden, Spain, the United Kingdom, Norway, and Switzerland. The countries reported seizing about 21,000 dose units (e...
March 2016: Drug Testing and Analysis
Dirk W Luchtman, Melissa J S Chee, Barbora Doslikova, Daniel L Marks, Vickie E Baracos, William F Colmers
Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR), remaining as lean as individuals who were naïve to HED. Other individuals become obese during HED exposure and subsequently defend the obese weight (Diet-Induced Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy diet. We hypothesized that the body weight setpoint of the DIO-D phenotype resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic melanocortins, including melanotan II (MTII), increase presynaptic GABA release, and the orexigenic neuropeptide Y (NPY) inhibits it...
2015: PloS One
Brent M Molden, Kimberly A Cooney, Kirk West, Lex H T Van Der Ploeg, Giulia Baldini
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in the brain, where it controls energy balance through pathways including α-melanocyte-stimulating hormone (α-MSH)-dependent signaling. We have reported that the MC4R can exist in an active conformation that signals constitutively by increasing cAMP levels in the absence of receptor desensitization. We asked whether synthetic MC4R agonists differ in their ability to increase intracellular cAMP over time in Neuro2A cells expressing endogenous MC4R and exogenous, epitope-tagged hemagglutinin-MC4R-green fluorescent protein...
November 2015: Molecular Endocrinology
Zhigang Shi, Baoxin Li, Virginia L Brooks
Leptin binds to receptors in multiple hypothalamic nuclei to increase sympathetic nerve activity; however, the neurocircuitry is unclear. Here, using anesthetized male Sprague-Dawley rats, we investigated the role of the paraventricular nucleus of the hypothalamus. Intracerebroventricular injection of leptin slowly increased lumbar sympathetic nerve activity (LSNA), heart rate, mean arterial pressure, and baroreflex control of LSNA and heart rate. Inhibition of the paraventricular nucleus with muscimol completely reversed leptin's effects...
November 2015: Hypertension
Eugenia Mc Allister, Gustavo Pacheco-Lopez, Stephen C Woods, Wolfgang Langhans
Insulin inhibits eating after its intracerebroventricular (ICV) administration in multiple species and under a variety of conditions. Nevertheless, the results across reports are inconsistent in that ICV insulin does not always reduce food intake. The reasons for this variability are largely unknown. Using mice as a model, we performed several crossover trials with insulin vs. vehicle when infused into the third cerebral ventricle (i3vt) to test the hypothesis that recent experience with the i3vt procedure contributes to the variability in the effect of ICV insulin on food intake...
November 1, 2015: Physiology & Behavior
C Bayerl
BACKGROUND: Homogenous pigmentation can be induced by α-melanocyte-stimulating hormone (MSH) homologues. Cosmetically inacceptable pigmentation is mostly located on the face. OBJECTIVES: Although afamelatonide is a prescription drug for the orphan disease erthropoetic protoporphyria, structurally related α-MSH derivatives are available via the internet. Preventive and therapeutical options are necessary for postinflammatory hyperpigmentation, melasma, and lentigines...
October 2015: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
C E Barrett, S E Arambula, L J Young
Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1-14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified...
July 21, 2015: Translational Psychiatry
Montserrat Navarro, Francisca Carvajal, Jose Manuel Lerma-Cabrera, Inmaculada Cubero, Mitchell J Picker, Todd E Thiele
BACKGROUND: The nonselective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol [EtOH]) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent preclinical evidence shows that MC receptor (MCR) agonists reduce excessive EtOH drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and the opioid systems in the modulation of pain, drug tolerance, and food intake...
August 2015: Alcoholism, Clinical and Experimental Research
Liqian Gao, Zhiqiang Yu, Dan Meng, Fang Zheng, Yong S Ong, Peng Miao, Su S Lee, Longping Wen
An α-MSH peptide analogue, named MTII (Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]- NH2), is one of the most important ligands of melanotropic receptors but are relatively nonselective. In order to improve the melanotropic activities of the well-characterized MTII analogues, we report here a new analogue by modifying the core structure as well as the size of the cyclic region of MTII peptide. The analogue peptide, Ac-Nle-c[Asp-His-D-Phe-Lys-Trp-Gly-Lys]-OH (F Peptide), in which we replaced Arg at position 8 with Lys and added a Gly to position 10 of the MTII peptide sequence, was synthesized and used as a new melanotropic hormone in controlling rapid color changes in frogs by its actions on mobilizing pigment granule movements within chromatophores...
2015: Protein and Peptide Letters
Gretchen M Sprow, Jennifer A Rinker, Emily G Lowery-Gointa, Angela M Sparrow, Montserrat Navarro, Todd E Thiele
Binge ethanol drinking is a highly pervasive and destructive behavior yet the underlying neurobiological mechanisms remain poorly understood. Recent work suggests that overlapping neurobiological mechanisms modulate feeding disorders and excessive ethanol intake, and converging evidence indicates that the melanocortin (MC) system may be a promising candidate. The aims of the present work were to examine how repeated binge-like ethanol drinking, using the 'drinking in the dark' (DID) protocol, impacts key peptides within the MC system and if site-specific manipulation of MC receptor (MCR) signaling modulates binge-like ethanol drinking...
July 2016: Addiction Biology
Meera E Modi, Kiyoshi Inoue, Catherine E Barrett, Kara A Kittelberger, Daniel G Smith, Rainer Landgraf, Larry J Young
The central melanocortin (MC) system has been widely studied for its effects on food intake and sexual behavior. However, the MC system, and more specifically the MC4 receptor (MC4R), also interacts with neurochemical systems that regulate socioemotional behaviors, including oxytocin (OT) and dopamine. In monogamous prairie voles, OT and dopamine interact to promote partner preference formation, a laboratory measure of an enduring social bond between mates. Here we investigated the effects of MC receptor activation on partner preference formation in prairie voles, as well as the interaction between the MC and OT systems during this process...
July 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Carlos A Campos, Hiroko Shiina, Robert C Ritter
Injection of the melanocortin-3/4 receptor agonist melanotan-II (MTII) into the nucleus of the solitary tract (NTS) produces rapid and sustained reduction of food intake. Melanocortin-4 receptors (MC4Rs) are expressed by vagal afferent endings in the NTS, but it is not known whether these endings participate in MTII-induced reduction of food intake. In experiments described here, we evaluated the contribution of central vagal afferent endings in MTII-induced reduction of food intake. Examination of rat hindbrain sections revealed that neuronal processes expressing immunoreactivity for the endogenous MC4R agonist α-melanoctyte-stimulating hormone course parallel and wrap around anterogradely labeled vagal afferent endings in the NTS and thus are aptly positioned to activate vagal afferent MC4Rs...
September 17, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Thomas H Meek, Miles E Matsen, Vincent Damian, Alex Cubelo, Streamson C Chua, Gregory J Morton
Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119...
November 2014: Endocrinology
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