Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

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. (Hepatology Communications 2018;2:644‐653)

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study

“…Hepatocytes constitute the major parenchymal iron storage pool and contain large amounts of ferritin, the primary iron storage protein [35]. Iron is an essential but potentially toxic element that may promote the onset and progression of NAFLD by increasing oxidative stress and altering insulin signaling and lipid metabolism [14,15,36,37]. Iron overload is observed in approximately one-third of adults with NAFLD [38].…”

“…The liver is the major iron storage organ and plays a key role in the metabolism of this nutrient [13]. Thus, iron has been involved in cellular oxidative stress and IR, key features of NAFLD pathogenesis, and hepatic iron accumulation has been linked to advanced fibrosis [14,15]. Ferritin is the chief iron storage protein but also is an acute-phase protein, and serum concentrations are increased in inflammatory conditions [16].…”

Antioxidant, iron chelating, lipase inhibition activities and metabolite’s prediction of hyrdoethanolic leaf extract of Conocarpus erectus

“…The exact FULL PAPER mode of action of iron in DMT2 initiation is not fully known but it has been reported that excess iron may damage beta cell of pancreas and also develop insulin insensitivity (Simcox and McClain, 2013). Similarly, the function of liver was also reported to be disturbed under iron load conditions which in turn affected glucose homeostasis and iron extraction (Britton et al, 2018). The Fe-chelating activity by plants extracts indicated that this capacity may be another mechanized reason behind the antidiabetic role of C. erectus leaves.…”

Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden

“…This unfavorable outcome suggests that the multiplexed platform may suffer from high false discovery rate, where the observed fold change may reflect technical inconsistency as discussed in our evaluation of the intra-assay reproducibility. To date, seven studies have used similar Quantibody® arrays at smaller scales to measure a range of six to 320 proteins simultaneously in the serum of various diseases [37][38][39][40] . Notably, Green et al used a Quantibody® array to concurrently examine the level of 10 cytokines in the serum of head and neck squamous cell carcinoma patients (n=101) taken before and after tumor treatment 37 .…”