Author information
1
Gallipoli Medical Research Institute Greenslopes Private Hospital Greenslopes Australia.
2
University of Queensland Herston Australia.
3
Department of Gastroenterology Princess Alexandra Hospital Woolloongabba Australia.
4
QIMR Berghofer Medical Research Institute Brisbane Australia.
5
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Maastricht the Netherlands.
6
Medical School, Faculty of Health Sciences University of Western Australia Crawley Australia.
7
Institute of Health and Biomedical Innovation and School of Biomedical Sciences Queensland University of Technology Kelvin Grove Australia.
8
Department of Hepatology Sir Charles Gairdner Hospital Perth Australia.
9
School of Physics University of Western Australia Crawley Australia.
10
Separation Science and Metabolomics Laboratory (Metabolomics Australia, Western Australia node) Murdoch University Murdoch Australia.
11
Department of Gastroenterology Fiona Stanley and Fremantle Hospital Group Murdoch Australia.
12
School of Health and Medical Sciences Edith Cowan University Joondalup Australia.
Abstract
Rodent and cell-culture models support a role for iron-related adipokine dysregulation and insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD); however, substantial human data are lacking. We examined the relationship between measures of iron status, adipokines, and insulin resistance in patients with NAFLD in the presence and absence of venesection. This study forms part of the Impact of Iron on Insulin Resistance and Liver Histology in Nonalcoholic Steatohepatitis (IIRON2) study, a prospective randomized controlled trial of venesection for adults with NAFLD. Paired serum samples at baseline and 6 months (end of treatment) in controls (n = 28) and patients who had venesection (n = 23) were assayed for adiponectin, leptin, resistin, retinol binding protein-4, tumor necrosis factor α, and interleukin-6, using a Quantibody, customized, multiplexed enzyme-linked immunosorbent assay array. Hepatic iron concentration (HIC) was determined using MR FerriScan. Unexpectedly, analysis revealed a significant positive correlation between baseline serum adiponectin concentration and HIC, which strengthened after correction for age, sex, and body mass index (rho = 0.36; P = 0.007). In addition, there were significant inverse correlations between HIC and measures of insulin resistance (adipose tissue insulin resistance (Adipo-IR), serum insulin, serum glucose, homeostasis model assessment of insulin resistance, hemoglobin A1c, and hepatic steatosis), whereas a positive correlation was noted with the insulin sensitivity index. Changes in serum adipokines over 6 months did not differ between the control and venesection groups. Conclusion: HIC positively correlates with serum adiponectin and insulin sensitivity in patients with NAFLD. Further study is required to establish causality and mechanistic explanations for these associations and their relevance in the pathogenesis of insulin resistance and NAFLD.