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      Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System

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          Abstract

          Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.

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          Most cited references44

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          Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity.

          Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity. Group 2 innate lymphoid cells (ILC2s) can regulate adaptive immunity and eosinophil and alternatively activated macrophage responses, and were recently identified in murine white adipose tissue (WAT) where they may act to limit the development of obesity. However, ILC2s have not been identified in human adipose tissue, and the mechanisms by which ILC2s regulate metabolic homeostasis remain unknown. Here we identify ILC2s in human WAT and demonstrate that decreased ILC2 responses in WAT are a conserved characteristic of obesity in humans and mice. Interleukin (IL)-33 was found to be critical for the maintenance of ILC2s in WAT and in limiting adiposity in mice by increasing caloric expenditure. This was associated with recruitment of uncoupling protein 1 (UCP1)(+) beige adipocytes in WAT, a process known as beiging or browning that regulates caloric expenditure. IL-33-induced beiging was dependent on ILC2s, and IL-33 treatment or transfer of IL-33-elicited ILC2s was sufficient to drive beiging independently of the adaptive immune system, eosinophils or IL-4 receptor signalling. We found that ILC2s produce methionine-enkephalin peptides that can act directly on adipocytes to upregulate Ucp1 expression in vitro and that promote beiging in vivo. Collectively, these studies indicate that, in addition to responding to infection or tissue damage, ILC2s can regulate adipose function and metabolic homeostasis in part via production of enkephalin peptides that elicit beiging.
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            The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness.

            Sleep and wakefulness are regulated to occur at appropriate times that are in accordance with our internal and external environments. Avoiding danger and finding food, which are life-essential activities that are regulated by emotion, reward and energy balance, require vigilance and therefore, by definition, wakefulness. The orexin (hypocretin) system regulates sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis.
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              Adipokines as emerging mediators of immune response and inflammation.

              The scientific interest in the biology of white adipose tissue (WAT) has increased since the discovery of leptin in 1994. The description of the product of the gene obese (ob) demonstrated the role of adipose tissue in the physiopathology of obesity-related diseases, and helped to increase the identification of numerous other adipokines, many of a pro-inflammatory nature. It has become increasingly evident that WAT-derived adipokines can be considered as a hub between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events that lead to metabolic syndrome, inflammatory and/or autoimmune conditions, and rheumatic diseases. In this Review, we will discuss the progress in adipokine research, focusing particular attention to the roles of leptin, adiponectin, resistin, visfatin, and other recently identified adipokines in inflammatory, autoimmune and rheumatic diseases.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                24 July 2018
                2018
                : 9
                : 982
                Affiliations
                [1] 1Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Università degli Studi della Campania “Luigi Vanvitelli” , Caserta, Italy
                [2] 2Dipartimento di Scienze Cardio-Toraciche e Respiratorie, Università degli Studi della Campania “Luigi Vanvitelli” , Naples, Italy
                [3] 3Sezione di Fisiologia Umana e Unità di Dietetica e Medicina dello Sport, Dipartimento di Medicina Sperimentale, Università degli Studi della Campania “Luigi Vanvitelli” , Naples, Italy
                [4] 4CEINGE-Biotecnologie Avanzate s.c. a r.l. , Naples, Italy
                [5] 5Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy
                [6] 6Department of Clinical and Experimental Medicine, University of Foggia , Foggia, Italy
                [7] 7Department of Anatomy, University of Malta , Msida, Malta
                Author notes

                Edited by: Giovanni Li Volti, Università degli Studi di Catania, Italy

                Reviewed by: Sonia Emanuele, Università degli Studi di Palermo, Italy; Marianna Lauricella, Università degli Studi di Palermo, Italy

                *Correspondence: Aurora Daniele, aurora.daniele@ 123456unicampania.it Giovanni Messina, giovanni.messina@ 123456unifg.it

                This article was submitted to Integrative Physiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2018.00982
                6094989
                30140232
                3e4c0407-fa11-4591-b8c5-d058b106a1e7
                Copyright © 2018 Polito, Nigro, Messina, Monaco, Monda, Scudiero, Cibelli, Valenzano, Picciocchi, Zammit, Pisanelli, Monda, Cincione, Daniele and Messina.

                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) and the copyright owner(s) 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
                : 06 June 2018
                : 03 July 2018
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 53, Pages: 6, Words: 0
                Categories
                Physiology
                Review

                Anatomy & Physiology
                adiponectin,orexin-a,immunity,adipose tissue,central nervous system
                Anatomy & Physiology
                adiponectin, orexin-a, immunity, adipose tissue, central nervous system

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