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      Allograft inflammatory factor 1 (AIF-1) is a new human adipokine involved in adipose inflammation in obese women

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          Abstract

          Background

          Allograft inflammatory factor 1 (AIF-1) is a putative obesity gene. Our aim was to examine the expression of AIF-1 in human white adipose tissue (WAT) in relation to obesity and metabolic phenotypes in women.

          Methods

          WAT secretion of AIF-1 was determined in subcutaneous adipose tissue pieces in vitro by ELISA from 5 subjects. mRNA expression of AIF-1 was determined by RT-qPCR in the isolated cell fractions of adipose tissue (n = 5-6 per group), in subcutaneous and visceral WAT pieces from non-obese (n = 12) and obese women (n = 23), and in some subcutaneous WAT also before and after weight reduction (n = 10). Finally, adipose AIF-1 mRNA was related to metabolic phenotypes in 96 subjects with a wide range of BMI.

          Results

          AIF-1 was secreted in a time dependent fashion from WAT. The major source of AIF-1 was WAT resident macrophages. Expression of AIF-1 was similar in visceral and subcutaneous WAT and was two-fold increased in obese women (P < 0.01). AIF-1 mRNA expression levels were normalized after weight reduction (P < 0.01). Expression of AIF-1 was inversely correlated with insulin sensitivity as assessed by insulin tolerance test (KITT), and circulating levels of adiponectin (P = 0.02), and positively correlated with insulin resistance as estimated by HOMA (=0.0042).

          Conclusions

          AIF-1 is a novel adipokine produced mainly by macrophages within human WAT. Its expression is increased in obese women and associates with unfavourable metabolic phenotypes. AIF-1 may play a paracrine role in the regulation of WAT function through cross-talk between macrophages and other cell types within the adipose tissue.

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          Most cited references25

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          Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity.

          To evaluate whether the homeostasis model assessment (HOMA) is a reliable surrogate measure of in vivo insulin sensitivity in humans. In the present study, we compared insulin sensitivity as assessed by a 4-h euglycemic (approximately 5 mmol/l) hyperinsulinemic (approximately 300 pmol/l) clamp with HOMA in 115 subjects with various degrees of glucose tolerance and insulin sensitivity. We found a strong correlation between clamp-measured total glucose disposal and HOMA-estimated insulin sensitivity (r = -0.820, P<0.0001), with no substantial differences between men (r = -0.800) and women (r = -0.796), younger (aged <50 years, r = -0.832) and older (r = -0.800) subjects, nonobese (BMI <27 kg/m2, r = -0.800) and obese (r = -0.765) subjects, nondiabetic (r = -0.754) and diabetic (r = -0.695) subjects, and normotensive ( r = -0.786) and hypertensive (r = -0.762) subjects. Also, we found good agreement between the two methods in the categorization of subjects according to insulin sensitivity (weighted k = 0.63). We conclude that the HOMA can be reliably used in large-scale or epidemiological studies in which only a fasting blood sample is available to assess insulin sensitivity
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            Dipeptidyl Peptidase 4 Is a Novel Adipokine Potentially Linking Obesity to the Metabolic Syndrome

            OBJECTIVE Comprehensive proteomic profiling of the human adipocyte secretome identified dipeptidyl peptidase 4 (DPP4) as a novel adipokine. This study assessed the functional implications of the adipokine DPP4 and its association to the metabolic syndrome. RESEARCH DESIGN AND METHODS Human adipocytes and skeletal and smooth muscle cells were used to monitor DPP4 release and assess the effects of soluble DPP4 on insulin signaling. In lean and obese subjects, depot-specific expression of DPP4 and its release from adipose tissue explants were determined and correlated to parameters of the metabolic syndrome. RESULTS Fully differentiated adipocytes exhibit a substantially higher release of DPP4 compared with preadipocytes or macrophages. Direct addition of DPP4 to fat and skeletal and smooth muscle cells impairs insulin signaling. A fivefold higher level of DPP4 protein expression was seen in visceral compared with subcutaneous fat of obese patients, with no regional difference in lean subjects. DPP4 serum concentrations significantly correlated with adipocyte size. By using adipose tissue explants from lean and obese subjects, we observed a twofold increase in DPP4 release that strongly correlated with adipocyte volume and parameters of the metabolic syndrome and was decreased to the lean level after weight reduction. DPP4 released from adipose tissue correlated positively with an increasing risk score for the metabolic syndrome. CONCLUSIONS DPP4 is a novel adipokine that may impair insulin sensitivity in an autocrine and paracrine fashion. Furthermore, DPP4 release strongly correlates with adipocyte size, potentially representing an important source of DPP4 in obesity. Therefore, we suggest that DPP4 may be involved in linking adipose tissue and the metabolic syndrome.
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              Adipose Tissue MicroRNAs as Regulators of CCL2 Production in Human Obesity

              In obesity, white adipose tissue (WAT) inflammation is linked to insulin resistance. Increased adipocyte chemokine (C-C motif) ligand 2 (CCL2) secretion may initiate adipose inflammation by attracting the migration of inflammatory cells into the tissue. Using an unbiased approach, we identified adipose microRNAs (miRNAs) that are dysregulated in human obesity and assessed their possible role in controlling CCL2 production. In subcutaneous WAT obtained from 56 subjects, 11 miRNAs were present in all subjects and downregulated in obesity. Of these, 10 affected adipocyte CCL2 secretion in vitro and for 2 miRNAs (miR-126 and miR-193b), regulatory circuits were defined. While miR-126 bound directly to the 3′-untranslated region of CCL2 mRNA, miR-193b regulated CCL2 production indirectly through a network of transcription factors, many of which have been identified in other inflammatory conditions. In addition, overexpression of miR-193b and miR-126 in a human monocyte/macrophage cell line attenuated CCL2 production. The levels of the two miRNAs in subcutaneous WAT were significantly associated with CCL2 secretion (miR-193b) and expression of integrin, α-X, an inflammatory macrophage marker (miR-193b and miR-126). Taken together, our data suggest that miRNAs may be important regulators of adipose inflammation through their effects on CCL2 release from human adipocytes and macrophages.
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                Author and article information

                Contributors
                Journal
                BMC Endocr Disord
                BMC Endocr Disord
                BMC Endocrine Disorders
                BioMed Central
                1472-6823
                2013
                25 November 2013
                : 13
                : 54
                Affiliations
                [1 ]Department of Medicine Huddinge, Lipid Laboratory, Novum, Karolinska Institutet, Karolinska University Hospital, SE-141 86 Huddinge, Stockholm, Sweden
                [2 ]Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut des maladies cardiovasculaires et métaboliques, Université Toulouse III Paul-Sabatier, Toulouse, France
                Article
                1472-6823-13-54
                10.1186/1472-6823-13-54
                4175115
                24267103
                1da67c4f-0014-44ad-aa16-f1b4d6eb5cf0
                Copyright © 2013 Lorente-Cebrián et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2013
                : 20 August 2013
                Categories
                Research Article

                Endocrinology & Diabetes
                aif-1,adipokines,obesity,adipose tissue
                Endocrinology & Diabetes
                aif-1, adipokines, obesity, adipose tissue

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