China
Africa
Explore chapters and articles related to this topic
The Genetic Alibi
Published in Roy J. Shephard, Obesity: A Kinesiologist’s Perspective, 2018
Some of the genes at the relevant loci produce substances that are highly expressed in the central nervous system, particularly in the arcuate nucleus of the hypothalamus. These regions of the brain are known to influence appetite, satiety, energy expenditures, and behavioural patterns [46]. Thus, the fat mass and obesity-associated protein FTO is found in parts of the brain that govern energy balance [20] and feeding behaviour [19]; it is encoded by the FTO gene on chromosome 16, and its presence in the hypothalamus is up-regulated following food deprivation. The melanocortin receptor MC4R is encoded by the MC4R gene; studies in mice have shown that its disruption causes hyperphagia, hyperinsulinaemia, and hyperglycaemia [22]. SH2B1 is an adapter protein involved in various signalling pathways; it increases serum levels of leptin [26], and disruption of the SH2B1 gene leads to hunger and insulin resistance. Other genes act peripherally, mainly in adipose tissue. The gene-encoding transcription factor AP2B (TFAP2B), for example, influences glucose transport, lipid accumulation, and adiponectin expression [22], the gene-encoding transcription factor cMAF is involved in adipogenesis [32], and the gene for natural cytotoxicity-triggering receptor 3 (NCR3) probably mediates its effects by causing a low-grade inflammation of adipose tissue [45].
The melanocyte and melaninogenesis
Published in Dimitris Rigopoulos, Alexander C. Katoulis, Hyperpigmentation, 2017
Dimitrios Xekardakis, Sabine Krueger-Krasagakis, Konstantinos Krasagakis
PKC-β is involved in the stabilization of tyrosinase and the increase of its enzymatic activity by phosphorylating serine residues on the cytoplasmic domain of tyrosinase. This process seems to lead to the formation of a complex between tyrosinase and TRP-1, which results, as mentioned in the previous paragraph, in the activation and stabilization of tyrosinase. Two further proteins that regulate melaninogenesis are the transcription factor MITF and the melanocortin 1 receptor (MC1R). MITF is very important for the survival of the melanocyte. It is a basic helix–loop–helix and leucine zipper transcription factor, and it has at least nine isoforms. MITF blocks the apoptotic process by enhancing the expression of BCL2, a major antiapoptotic protein in the cell.21 Additionally, it regulates the transcription of the most important melaninogenesis enzymes, PKC-β, tyrosinase, TRP-1, and TRP-2. More specifically, transcription of PKC-β and tyrosinase is controlled by the MITF-M isoform.22 MC1R is the first of the five proteins that belong to the family of the melanocortin receptors, which are G protein–coupled receptors.9 The remaining are MC2R, MC3R, MC4R, and MC5R. Each of them has seven transmembrane domains. MC1R is expressed mostly in melanocytes, but also in other types of cells (keratinocytes, fibroblasts, and endothelial cells).8 It is activated by the hormones ACTH and α-MSH. MC1R regulates melaninogenesis by activating PKA, which induces MITF transcription, and then MITF, by the processes mentioned above, promotes synthesis of eumelanin.15
Vagal Afferent Signaling and the Integration of Direct and Indirect Controls of Food Intake
Published in Ruth B.S. Harris, Appetite and Food Intake, 2017
Robert C. Ritter, Carlos A. Campos, Jason Nasse, James H. Peters
Leptin excites POMC neurons in the ARC of the hypothalamus (Cowley et al. 2001, 2003). Activation of POMC neurons is associated with inhibition of food intake and body fat loss, primarily through activation of type 4 melanocortin receptors (MC4R) (recently reviewed in Koch and Horvath 2014). Although most attention has focused on melanocortinergic projections within the hypothalamus, Zheng et al. (2010) have reported that hindbrain injection of a melanocortin 3/4 receptor antagonist attenuates reduction of food intake following leptin injection into the ARC. These results suggest that hypothalamic melanocortinergic projections to the hindbrain are responsible, at least in part, for reduction of food intake by leptin. Of further interest are reports indicating that hindbrain MC4R receptors participate in control of meal size (Zheng et al. 2005) and reduction of food intake by CCK (Fan et al. 2004, Sutton et al. 2005). Specifically, injection of a melanocortin receptor agonist into the hindbrain reduces food intake by reducing meal size, and reduction of food intake following intraperitoneal injection of CCK is attenuated by hindbrain injection of an MC3/4 receptor antagonist. The foregoing results strongly suggest that melanocortin receptors in the hindbrain modulate GI signals that control food intake. Until very recently, however, specific cellular mechanisms for modulation of direct GI control by hindbrain melanocortin receptors were not identified.
A review on pharmacological options for the treatment of erectile dysfunction: state of the art and new strategies
Published in Expert Opinion on Pharmacotherapy, 2023
Mattia Longoni, Alessandro Bertini, Nicolò Schifano, Emanuele Zaffuto, Paolo Maggio, Rossi Piercarlo, Sara Baldini, Giulio Carcano, Gabriele Antonini, Andrea Salonia, Francesco Montorsi, Federico Dehò, Paolo Capogrosso
The contribution of the melanocortin system to sexual function is well known and pro-erectile functions of spinal melanocortin receptors, such as MC4R, have been proposed in multiple studies [103,104]. Indeed, intrathecal injection of melanocortin agonist (i.e. MT-II) to male rats’ lumbar spinal cord increases spontaneous erections [105]. Differently from ‘peripherical’ molecular pathways targeted by conventional drugs, MT-II manipulation of melanocortinergic receptors elicits a centrally-mediated erection by modulating the sympathetic efferent nerves to the pelvis, with little effect on the parasympathetics [106]. In a double-blind placebo-controlled study, MT-II peptide (0.025 mg/Kg) subcutaneous injection to 20 patients affected by psychogenic and organic ED was able to elicit significant erection in 17/20 men without video sex stimulation. Therefore, contrary to PDE5Is, MT-II agonist seems to induce spontaneous erection in absence of sexual stimulation [107]. Further clinical studies led to the development of PT−141, a cyclic heptapeptide melanocortin analog with improved tolerability, a more rapid onset of action compared to MT-II, and equal efficacy. In the phase IIA study, PT−141 intranasal administration induced a clinically significant erectile response compared to placebo [108,109]. Finally, in a pilot study the administration of a selective melanocortin−4 receptor agonist displayed a similar number of clinical responses to sildenafil [110]. Despite these preliminary promising results, which indicate melanocortin system as a novel target for ED treatment, further studies are needed.
Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis
Published in Ocular Immunology and Inflammation, 2022
Tat Fong Ng, Ambika Manhapra, David Cluckey, Yoona Choe, Srujan Vajram, Andrew W. Taylor
The neuropeptide α-MSH is part of the highly conserved melanocortin family of molecules that includes Adrenocorticotropic hormone (ACTH), and the five G-protein-coupled melanocortin receptors.13–15 While ACTH binds all five melanocortin receptors (MCr), α-MSH binds all but MC2r.15,16 The MC2r is exclusively expressed on the adrenal glands through which ACTH induces corticosteroid production. The melanocortin receptors MC1r, MC3r, and MC5r are expressed on immune cells, and cells of the retina.8,17–23 The literature demonstrates that there is differential regulation of immune cell activity through the different melanocortin receptors. The neuropeptide α-MSH through MC1r and MC3r suppresses pro-inflammatory activity in activated macrophages.21,24–27 Through MC5r, α-MSH promotes the induction of Treg cells and induces suppressor APC with the capacity in an antigen-specific manner to mediate counter-conversion of effector CD4+ T cells into Treg cells.8,18,22,28–31
Neurobehavioral and neuroendocrine regulation of energy homeostasis
Published in Postgraduate Medicine, 2019
Stavroula A. Paschou, Konstantinos I. Tsamis, Christina Kanaka-Gantenbein, Elizabeth O. Johnson, George P. Chrousos
During fasting, gastric cells release ghrelin that stimulates the NPY/AgRP neurons. In turn, these neurons activate other ones in the lateral and perifornical hypothalamic areas, which contain orexins and melanin-concentrating hormone (MCH), while they inhibit oxytocin release from paraventricular (PVN) nuclei, in order to evoke acute feeding [2,5]. Ghrelin also provides orexigenic signals to the brainstem via the area postrema [5]. In postprandial state, various hormonal changes occur and favor satiety. After insulin secretion by β pancreatic cells, leptin release by adipocytes and incretins secretion (including glucagon-like peptide 1, GLP-1) by intestine cells, these hormones are conveyed into the ARC, where they activate CART/POMC neurons [2,6]. α-Melanocyte-stimulating hormone (α-MSH) is then released and binded to melanocortin receptors in other hypothalamic regions. These lead to acute hypophagic phenomena, as well as increased energy expenditure [3].