Abstract

The novel adipokine chemerin has been related to insulin-resistant states such as obesity and non alcoholic fatty liver disease (NAFLD). However, its association with insulin resistance and beta cell function remains controversial. The main objective was to examine whether serum chemerin levels associate with insulin sensitivity and beta cell function independently of body mass index (BMI), by studying consecutive outpatients of the hepatology clinics of a European university hospital. Individuals (n=196) with NAFLD were stratified into persons with normal glucose tolerance (NGT; n=110), impaired glucose tolerance (IGT; n=51) and type 2 diabetes (T2D; n=35) and the association between serum chemerin and measures of insulin sensitivity and beta cell function as assessed during fasting and during oral glucose tolerance test (OGTT) was measured. Our results showed that serum chemerin positively associated with BMI (P=0.0007) and C peptide during OGTT (P<0.004), but not with circulating glucose, insulin, lipids or liver enzymes (all P>0.18). No BMI independent relationships of chemerin with fasting and OGTT derived measures of insulin sensitivity were found (P>0.5). Chemerin associated positively with fasting beta cell function as well as the OGTT derived insulinogenic index IGI_cp and the adaptation index after adjustment for age, sex and BMI (P=0.002-0.007), and inversely with the insulin/C peptide ratio (P=0.007). Serum chemerin neither related to the insulinogenic index IGI_ins nor the disposition index. In conclusion, circulating chemerin is likely linked to enhanced beta cell function but not to insulin sensitivity in patients with NAFLD.

Highlights

  • Chemerin is highly expressed in white adipose tissue, liver and lungs, secreted as inactive prochemerin and binds after activation to the chemokine—like receptor 1 (CMKLR1) [1,2]

  • Except from younger age in normal glucose tolerance (NGT) compared with impaired glucose tolerance (IGT) and type 2 diabetes (T2D), the groups did not differ with respect to sex, body mass index (BMI) as well as serum lipids and transaminases

  • This study shows that circulating chemerin concentrations positively associate with BMI in patients with non alcoholic fatty liver disease (NAFLD), but are higher in individuals with IGT or type 2 diabetes compared to NGT in this study population

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Summary

Introduction

Chemerin is highly expressed in white adipose tissue, liver and lungs, secreted as inactive prochemerin and binds after activation to the chemokine—like receptor 1 (CMKLR1) [1,2]. Binding of chemerin to CMKLR1 in immune cells and adipose tissue stimulates chemotaxis at sites of inflammation [3,4]. Previous studies in humans suggested that chemerin is increased and/or associates with age [3,5], degree of adiposity based on body mass index (BMI) or fat mass and obesity-related markers such as leptin and resistin [3,6,7,8,9,10]. Likewise, circulating chemerin tended to be positively associated with HOMA-β as a surrogate marker of fasting insulin secretion in Japanese patients with metabolic syndrome or type 2 diabetes [20]

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