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      Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

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          Abstract

          Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. This study aims to review the crosstalk between adipokines, myokines, and hepatokines. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.

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          Most cited references114

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          Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies

          The prevalence of obesity in combination with sarcopenia (the age-related loss of muscle mass and strength or physical function) is increasing in adults aged 65 years and older. A major subset of adults over the age of 65 is now classified as having sarcopenic obesity, a high-risk geriatric syndrome predominantly observed in an ageing population that is at risk of synergistic complications from both sarcopenia and obesity. This Review discusses pathways and mechanisms leading to muscle impairment in older adults with obesity. We explore sex-specific hormonal changes, inflammatory pathways and myocellular mechanisms leading to the development of sarcopenic obesity. We discuss the evolution, controversies and challenges in defining sarcopenic obesity and present current body composition modalities used to assess this condition. Epidemiological surveys form the basis of defining its prevalence and consequences beyond comorbidity and mortality. Current treatment strategies, and the evidence supporting them, are outlined, with a focus on calorie restriction, protein supplementation and aerobic and resistance exercises. We also describe weight loss-induced complications in patients with sarcopenic obesity that are relevant to clinical management. Finally, we review novel and potential future therapies including testosterone, selective androgen receptor modulators, myostatin inhibitors, ghrelin analogues, vitamin K and mesenchymal stem cell therapy.
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            Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance

            In this Review, the authors describe the factors that influence the development of hepatic steatosis and discuss the evidence base that links steatosis to insulin resistance. They explore how steatosis alters the secretion of hepatokines from the liver, and how these secretome alterations regulate glucose metabolism and insulin action in non-hepatic tissues.
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              Physical activity and muscle–brain crosstalk

              Neurological and mental illnesses account for a considerable proportion of the global burden of disease. Exercise has many beneficial effects on brain health, contributing to decreased risks of dementia, depression and stress, and it has a role in restoring and maintaining cognitive function and metabolic control. The fact that exercise is sensed by the brain suggests that muscle-induced peripheral factors enable direct crosstalk between muscle and brain function. Muscle secretes myokines that contribute to the regulation of hippocampal function. Evidence is accumulating that the myokine cathepsin B passes through the blood-brain barrier to enhance brain-derived neurotrophic factor production and hence neurogenesis, memory and learning. Exercise increases neuronal gene expression of FNDC5 (which encodes the PGC1α-dependent myokine FNDC5), which can likewise contribute to increased brain-derived neurotrophic factor levels. Serum levels of the prototype myokine, IL-6, increase with exercise and might contribute to the suppression of central mechanisms of feeding. Exercise also increases the PGC1α-dependent muscular expression of kynurenine aminotransferase enzymes, which induces a beneficial shift in the balance between the neurotoxic kynurenine and the neuroprotective kynurenic acid, thereby reducing depression-like symptoms. Myokine signalling, other muscular factors and exercise-induced hepatokines and adipokines are implicated in mediating the exercise-induced beneficial impact on neurogenesis, cognitive function, appetite and metabolism, thus supporting the existence of a muscle-brain endocrine loop.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                05 March 2021
                March 2021
                : 22
                : 5
                : 2639
                Affiliations
                [1 ]Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho 1001, Marília 17525-902, São Paulo, Brazil; anaritasantos@ 123456hotmail.com (A.R.d.O.d.S.); barbarazanuzo@ 123456hotmail.com (B.d.O.Z.); vitormiola@ 123456hotmail.com (V.F.B.M.); patriciabueno@ 123456hotmail.com (P.C.S.B.); uriflato@ 123456hotmail.com (U.A.P.F.); danibuchaim@ 123456hotmail.com (D.V.B.); ricardotofano@ 123456hotmail.com (R.J.T.); claudemirmendes@ 123456hotmail.com (C.G.M.); vivianetofano@ 123456gmail.com (V.A.C.T.); jesselinahaber@ 123456hotmail.com (J.F.d.S.H.)
                [2 ]Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenida Hygino Muzzy Filho 1001, Marília 17525-902, São Paulo, Brazil; claudiarucco@ 123456gmail.com
                [3 ]Department of Biochemistry and Nutrition, Faculty of Food Technology of Marília, Marília 17500-000, São Paulo, Brazil
                [4 ]Department of Animal Sciences, School of Veterinary Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho 1001, Marília 17525-902, São Paulo, Brazil
                [5 ]Medical School, University Center of Adamantina (UniFAI), Adamantina 17800-000, São Paulo, Brazil
                [6 ]Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (FOB–USP), Alameda Doutor Octávio Pinheiro Brisolla 9-75, Bauru 17040, São Paulo, Brazil; rogerioLeone@ 123456hotmail.com
                Author notes
                [* ]Correspondence: smbarbalho@ 123456gmail.com ; Tel.: 55-14-99655-3190
                Author information
                https://orcid.org/0000-0002-5035-876X
                Article
                ijms-22-02639
                10.3390/ijms22052639
                7961600
                33807959
                fe482e9a-c45e-4e13-bf2d-908adf292dd4
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 January 2021
                : 02 March 2021
                Categories
                Review

                Molecular biology
                adipokines,myokines,hepatokines,metabolism,cardiovascular diseases
                Molecular biology
                adipokines, myokines, hepatokines, metabolism, cardiovascular diseases

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