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      Oxygenation of adipose tissue: A human perspective

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          Abstract

          Obesity is a complex disorder of excessive adiposity, and is associated with adverse health effects such as cardiometabolic complications, which are to a large extent attributable to dysfunctional white adipose tissue. Adipose tissue dysfunction is characterized by adipocyte hypertrophy, impaired adipokine secretion, a chronic low‐grade inflammatory status, hormonal resistance and altered metabolic responses, together contributing to insulin resistance and related chronic diseases. Adipose tissue hypoxia, defined as a relative oxygen deficit, in obesity has been proposed as a potential contributor to adipose tissue dysfunction, but studies in humans have yielded conflicting results. Here, we will review the role of adipose tissue oxygenation in the pathophysiology of obesity‐related complications, with a specific focus on human studies. We will provide an overview of the determinants of adipose tissue oxygenation, as well as the role of adipose tissue oxygenation in glucose homeostasis, lipid metabolism and inflammation. Finally, we will discuss the putative effects of physiological and experimental hypoxia on adipose tissue biology and whole‐body metabolism in humans. We conclude that several lines of evidence suggest that alteration of adipose tissue oxygenation may impact metabolic homeostasis, thereby providing a novel strategy to combat chronic metabolic diseases in obese humans.

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          Most cited references143

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          Origin and physiological roles of inflammation.

          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.

            Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.
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              Adapting to obesity with adipose tissue inflammation

              Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Here, Reilly and Saltiel review the cellular and molecular mechanisms of obesity-induced inflammation in adipose tissue and discuss potential therapeutic approaches.
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                Author and article information

                Contributors
                G.Goossens@maastrichtuniversity.nl
                Journal
                Acta Physiol (Oxf)
                Acta Physiol (Oxf)
                10.1111/(ISSN)1748-1716
                APHA
                Acta Physiologica (Oxford, England)
                John Wiley and Sons Inc. (Hoboken )
                1748-1708
                1748-1716
                02 June 2019
                January 2020
                : 228
                : 1 ( doiID: 10.1111/apha.v228.1 )
                : e13298
                Affiliations
                [ 1 ] College of Medical and Dental Sciences, Institute of Metabolism and Systems Research (IMSR) University of Birmingham Birmingham UK
                [ 2 ] Centre for Endocrinology, Diabetes and Metabolism Birmingham Health Partners Birmingham UK
                [ 3 ] Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+ Maastricht the Netherlands
                Author notes
                [*] [* ] Correspondence

                Gijs H. Goossens, Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, PO Box 616, 6200 MD Maastricht, the Netherlands.

                Email: G.Goossens@ 123456maastrichtuniversity.nl

                Author information
                https://orcid.org/0000-0002-2092-3019
                Article
                APHA13298
                10.1111/apha.13298
                6916558
                31077538
                a8d3f1ad-11d5-4356-a33a-9406d212bbba
                © 2019 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 February 2019
                : 03 May 2019
                : 08 May 2019
                Page count
                Figures: 3, Tables: 2, Pages: 17, Words: 12671
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:17.12.2019

                Anatomy & Physiology
                adipose tissue,hypoxia,inflammation,metabolism,obesity,oxygen
                Anatomy & Physiology
                adipose tissue, hypoxia, inflammation, metabolism, obesity, oxygen

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