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      Associations of circulating chemerin and adiponectin concentrations with hepatic steatosis

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          Abstract

          Objective

          Chemerin and adiponectin are adipokines assumed to be involved in the development of metabolic syndrome-related phenotypes like hepatic steatosis. We aimed to evaluate the associations of circulating chemerin and adiponectin concentrations with liver enzymes, liver fat content, and hepatic steatosis in the general population.

          Methods

          Data of 3951 subjects from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Hepatic steatosis was assumed when either a hyperechogenic liver (assessed via ultrasound) or a magnetic resonance imaging (MRI)-quantified liver fat content >5% was present. Adjusted sex-specific quantile and logistic regression models were applied to analyze the associations of chemerin and adiponectin with liver enzymes, liver fat content and hepatic steatosis.

          Results

          The observed associations of chemerin and adiponectin with liver enzymes were very divergent depending on sex, fasting status and the specific enzyme. More consistent results were seen in the analyses of these adipokines in relation to MRI-quantified liver fat content. Here, we observed inverse associations to adiponectin in both sexes as well as a positive (men) or U-shaped (women) association to chemerin. Similarly, the MRI-based definition of hepatic steatosis revealed strongly consistent results: in both sexes, high chemerin concentrations were associated with higher odds of hepatic steatosis, whereas high adiponectin concentrations were associated with lower odds.

          Conclusion

          Our results suggest a role of these adipokines in the pathogenesis of hepatic steatosis independent of metabolic or inflammatory disorders. However, experimental studies are needed to further clarify the underlying mechanisms and the inter-play between adipokine concentrations and hepatic steatosis.

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          Most cited references38

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          Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background.

          The aim of this investigation was to elucidate the time-course of changes in the prevalence of fatty liver, and to analyze its clinical backgrounds over the previous 12-year period. Thirty-nine thousand one hundred and fifty-one individuals who visited the Tokai University Hospital Health Checkup Center from 1989 to 2000 were examined for the presence of fatty liver, and their clinical backgrounds were analyzed. In 1989, the prevalence of fatty liver was 12.6%, and it rose gradually thereafter, reaching 30.3% in 1998, corresponding to a 2.4-fold increase over the prevalence rate in 1989. The average prevalence was about twice as high in males (26.0%) as in females (12.7%). The prevalence was uniformly high in males in all ages, while the prevalence in females tended to rise gradually with age. Body mass index (BMI) was found to be the variable most closely related to the onset of fatty liver. On the other hand, nonobese individuals with a BMI of less than 25 kg/m(2) accounted for approximately half of all the patients with fatty liver, and this proportion remained almost unchanged during the 12-year survey period. It was therefore difficult to simply attribute the increase in the prevalence of fatty liver to the increased prevalence of obesity. In the 35 519 repeat examinees (repeaters), it was found that 5088 individuals (14.3%) developed fatty liver, and fatty liver resolved in 1248 individuals (3.5%). As fatty liver developed, the BMI increased by 1.0 +/- 1.3 kg/m(2). As fatty liver disappeared, the BMI decreased by 1.0 +/- 1.5 kg/m(2). These results suggest that the absolute value of the BMI, as well as the relative changes in the BMI in each individual, may be related to the onset of fatty liver. The aim of this investigation was to elucidate the time-course of changes in the prevalence of fatty liver, and to analyze its clinical backgrounds over the previous 12-year period.
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            Adipokines and cytokines in non-alcoholic fatty liver disease.

            Several adipocytokines have been implicated in the pathogenesis non-alcoholic fatty liver disease (NAFLD). To assess adipocytokines in NAFLD patients and controls. A total of 95 patients (26 non-alcoholic steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non-obese controls) were included. Fasting serum insulin, glucose, visfatin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used to compare groups and determine associations. Serum TNF-alpha and IL-8 were higher in NAFLD patients when compared with both obese and non-obese controls. Analysis involving all patients revealed a significant correlation between serum TNF-alpha and IL-8 (P < 6.319e-08), and between IL-6 and IL-8 (P < 5.271e-15). Homeostatic model assessment scores negatively correlated with adiponectin in NAFLD (P < 0.0032). Serum visfatin was higher in all three obese groups than in non-obese controls (P < 0.02, P < 0.002 and P < 0.008). Visfatin in NASH patients was lower than SS and obese controls. Although TNF-alpha was associated with NAFLD (P < 0.02), it was interdependent on visfatin. In comparison to SS, four factors were independently associated with NASH: age, alanine aminotransferase, IL-8 and adiponectin (P < 0.05). Multivariate analysis indicated that TNF-alpha was the only independent predictor of fibrosis in NASH (P < 0.0004). These findings support a complex interaction between adipocytokines and the pathogenesis of NAFLD.
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              Adipokines in liver diseases.

              Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                August 2019
                02 July 2019
                : 8
                : 8
                : 1097-1107
                Affiliations
                [1 ]Institute of Clinical Chemistry and Laboratory Medicine , University Medicine Greifswald, Greifswald, Germany
                [2 ]Institute for Community Medicine , University Medicine Greifswald, Greifswald, Germany
                [3 ]DZHK (German Centre for Cardiovascular Research) , Greifswald, Germany
                [4 ]DZD (German Center for Diabetes Research) , Greifswald, Germany
                [5 ]Department of Medicine A , University Medicine Greifswald, Greifswald, Germany
                [6 ]Department of Diagnostic Radiology and Neuroradiology , University Medicine Greifswald, Greifswald, Germany
                [7 ]Institute and Policlinic for Radiology and Interventional Radiology , University Hospital, Carl-Gustav-Carus University Dresden, Dresden, Germany
                Author notes
                Correspondence should be addressed to S Zylla: stephanie.zylla@ 123456med.uni-greifswald.de
                Article
                EC-19-0300
                10.1530/EC-19-0300
                6652250
                31265993
                733b8ab4-b5d4-48b9-ac4b-561fdd06c064
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 17 June 2019
                : 02 July 2019
                Categories
                Research

                adiponectin,chemerin,hepatic steatosis,liver fat content,liver enzymes

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