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      Appetite-Controlling Endocrine Systems in Teleosts

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          Abstract

          Mammalian studies have shaped our understanding of the endocrine control of appetite and body weight in vertebrates and provided the basic vertebrate model that involves central (brain) and peripheral signaling pathways as well as environmental cues. The hypothalamus has a crucial function in the control of food intake, but other parts of the brain are also involved. The description of a range of key neuropeptides and hormones as well as more details of their specific roles in appetite control continues to be in progress. Endocrine signals are based on hormones that can be divided into two groups: those that induce (orexigenic), and those that inhibit (anorexigenic) appetite and food consumption. Peripheral signals originate in the gastrointestinal tract, liver, adipose tissue, and other tissues and reach the hypothalamus through both endocrine and neuroendocrine actions. While many mammalian-like endocrine appetite-controlling networks and mechanisms have been described for some key model teleosts, mainly zebrafish and goldfish, very little knowledge exists on these systems in fishes as a group. Fishes represent over 30,000 species, and there is a large variability in their ecological niches and habitats as well as life history adaptations, transitions between life stages and feeding behaviors. In the context of food intake and appetite control, common adaptations to extended periods of starvation or periods of abundant food availability are of particular interest. This review summarizes the recent findings on endocrine appetite-controlling systems in fish, highlights their impact on growth and survival, and discusses the perspectives in this research field to shed light on the intriguing adaptations that exist in fish and their underlying mechanisms.

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          Efficient In Vivo Genome Editing Using RNA-Guided Nucleases

          Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have evolved in bacteria and archaea as a defense mechanism to silence foreign nucleic acids of viruses and plasmids. Recent work has shown that bacterial type II CRISPR systems can be adapted to create guide RNAs (gRNAs) capable of directing site-specific DNA cleavage by the Cas9 nuclease in vitro. Here we show that this system can function in vivo to induce targeted genetic modifications in zebrafish embryos with efficiencies comparable to those obtained using ZFNs and TALENs for the same genes. RNA-guided nucleases robustly enabled genome editing at 9 of 11 different sites tested, including two for which TALENs previously failed to induce alterations. These results demonstrate that programmable CRISPR/Cas systems provide a simple, rapid, and highly scalable method for altering genes in vivo, opening the door to using RNA-guided nucleases for genome editing in a wide range of organisms.
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            Thyroid hormone regulation of metabolism.

            Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.
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              Leptin.

              The discovery of the adipose-derived hormone leptin has generated enormous interest in the interaction between peripheral signals and brain targets involved in the regulation of feeding and energy balance. Plasma leptin levels correlate with fat stores and respond to changes in energy balance. It was initially proposed that leptin serves a primary role as an anti-obesity hormone, but this role is commonly thwarted by leptin resistance. Leptin also serves as a mediator of the adaptation to fasting, and this role may be the primary function for which the molecule evolved. There is increasing evidence that leptin has systemic effects apart from those related to energy homeostasis, including regulation of neuroendocrine and immune function and a role in development.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                18 April 2017
                2017
                : 8
                : 73
                Affiliations
                [1] 1Department of Biology, University of Bergen , Bergen, Norway
                [2] 2Research Center for Aquaculture Systems, National Research Institute of Aquaculture, Japan Fisheries Research and Education Agency , Tamaki, Mie, Japan
                [3] 3Department of Biological and Environmental Sciences, University of Gothenburg , Gothenburg, Sweden
                [4] 4Departments of Biology and Biochemistry, Memorial University of Newfoundland , St John’s, NL, Canada
                Author notes

                Edited by: Maximilian Michel, University of Michigan, USA

                Reviewed by: Russell J. Borski, North Carolina State University, USA; José Luis Soengas, University of Vigo, Spain; Even Hjalmar Jørgensen, UiT the Arctic University of Norway, Norway

                *Correspondence: Ivar Rønnestad, ivar.ronnestad@ 123456bio.uib.no

                Specialty section: This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2017.00073
                5394176
                28458653
                ccd31c9f-c016-4333-8a92-fb443cd2ee71
                Copyright © 2017 Rønnestad, Gomes, Murashita, Angotzi, Jönsson and Volkoff.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 January 2017
                : 27 March 2017
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 425, Pages: 24, Words: 25232
                Funding
                Funded by: Norges Forskningsråd 10.13039/501100005416
                Award ID: 172548/S40, 199482, 190043
                Funded by: Seventh Framework Programme 10.13039/501100004963
                Award ID: KBBE-2007-2A LIFECYCLE
                Funded by: Natural Sciences and Engineering Research Council of Canada 10.13039/501100000038
                Award ID: Discovery Grant, 261414-03
                Funded by: Fisheries Agency 10.13039/501100004620
                Funded by: Japan Society for the Promotion of Science 10.13039/501100001691
                Award ID: KAKENHI (15K18745)
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                appetite control,feed intake,hormones,neuropeptides,teleosts,adaptations,fasting,voracious feeding

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