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      Hypoxanthine Secretion from Human Adipose Tissue and its Increase in Hypoxia : Hypoxanthine Secretion from Human Adipose Tissue

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          Abstract

          The production of uric acid in murine white adipose tissue (mWAT), and that such production was augmented in obese mice, was recently reported. However, little is known about the secretion of metabolites associated with purine catabolism in human WAT (hWAT). The present study analyzed this in hWAT.

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          Most cited references43

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          Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.

          A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.
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            Adipose tissue remodeling and obesity.

            To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth.
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              Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice.

              Chronic inflammation and reduced adiponectin are widely observed in the white adipose tissue in obesity. However, the cause of the changes remains to be identified. In this study, we provide experimental evidence that hypoxia occurs in adipose tissue in obese mice and that adipose hypoxia may contribute to the endocrine alterations. The adipose hypoxia was demonstrated by a reduction in the interstitial partial oxygen pressure (Po(2)), an increase in the hypoxia probe signal, and an elevation in expression of the hypoxia response genes in ob/ob mice. The adipose hypoxia was confirmed in dietary obese mice by expression of hypoxia response genes. In the adipose tissue, hypoxia was associated with an increased expression of inflammatory genes and decreased expression of adiponectin. In dietary obese mice, reduction in body weight by calorie restriction was associated with an improvement of oxygenation and a reduction in inflammation. In cell culture, inflammatory cytokines were induced by hypoxia in primary adipocytes and primary macrophages of lean mice. The transcription factor NF-kappaB and the TNF-alpha gene promoter were activated by hypoxia in 3T3-L1 adipocytes and NIH3T3 fibroblasts. In addition, adiponectin expression was reduced by hypoxia, and the reduction was observed in the gene promoter in adipocytes. These data suggest a potential role of hypoxia in the induction of chronic inflammation and inhibition of adiponectin in the adipose tissue in obesity.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Obesity
                Obesity
                Wiley
                19307381
                July 2018
                July 2018
                June 07 2018
                : 26
                : 7
                : 1168-1178
                Affiliations
                [1 ]Department of Metabolic Medicine, Graduate School of Medicine; Osaka University; Suita Osaka Japan
                [2 ]Department of Gastroenterological Surgery; Graduate School of Medicine, Osaka University; Suita Osaka Japan
                [3 ]Department of Biotechnology; Graduate School of Engineering, Osaka University; Suita Osaka Japan
                [4 ]Division of Metabolomics, Research Center for Transomics Medicine; Medical Institute of Bioregulation, Kyushu University; Fukuoka Japan
                [5 ]Teijin Institute for Bio-medical Research, Teijin Pharma Limited; Hino Tokyo Japan
                [6 ]Department of Metabolism and Atherosclerosis; Graduate School of Medicine, Osaka University; Suita Osaka Japan
                Article
                10.1002/oby.22202
                29877616
                18e224e7-ddd8-4706-adc9-3acf2fe12951
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

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