Hepatic Iron Concentration Correlates With Insulin Sensitivity in Nonalcoholic Fatty Liver Disease

Laurence Britton; Kim Bridle; Janske Reiling; Nishreen Santrampurwala; Leesa Wockner; Helena Ching; Katherine Stuart; V. Nathan Subramaniam; Gary Jeffrey; Tim St Pierre; Michael House; Joel Gummer; Robert Trengove; John Olynyk; Darrell Crawford; Leon Adams

doi:10.1002/hep4.1190

Hepatic Iron Concentration Correlates With Insulin Sensitivity in Nonalcoholic Fatty Liver Disease

Laurence Britton^*, Kim Bridle, Janske Reiling, Nishreen Santrampurwala, Leesa Wockner, Helena Ching, Katherine Stuart, V. Nathan Subramaniam, Gary Jeffrey, Tim St Pierre, Michael House, Joel Gummer, Robert Trengove, John Olynyk, Darrell Crawford, Leon Adams

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 alpha, and interleukin6, using a Qiantibody, 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 Alc, 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.

Original language	English
Pages (from-to)	644-653
Number of pages	10
Journal	Hepatology communications
Volume	2
Issue number	6
DOIs	https://doi.org/10.1002/hep4.1190
Publication status	Published - Jun 2018

Keywords

ADIPOSE-TISSUE
RESISTANCE
ADIPONECTIN
METABOLISM
OVERLOAD
OBESITY
HEMOCHROMATOSIS
EXPRESSION
HEPCIDIN
GLUCOSE

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Britton, L., Bridle, K., Reiling, J., Santrampurwala, N., Wockner, L., Ching, H., Stuart, K., Subramaniam, V. N., Jeffrey, G., St Pierre, T., House, M., Gummer, J., Trengove, R., Olynyk, J., Crawford, D., & Adams, L. (2018). Hepatic Iron Concentration Correlates With Insulin Sensitivity in Nonalcoholic Fatty Liver Disease. Hepatology communications, 2(6), 644-653. https://doi.org/10.1002/hep4.1190

@article{3be88d96a788495a9d55d2464b7b68c3,

title = "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 alpha, and interleukin6, using a Qiantibody, 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 Alc, 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.",

keywords = "ADIPOSE-TISSUE, RESISTANCE, ADIPONECTIN, METABOLISM, OVERLOAD, OBESITY, HEMOCHROMATOSIS, EXPRESSION, HEPCIDIN, GLUCOSE",

author = "Laurence Britton and Kim Bridle and Janske Reiling and Nishreen Santrampurwala and Leesa Wockner and Helena Ching and Katherine Stuart and Subramaniam, {V. Nathan} and Gary Jeffrey and {St Pierre}, Tim and Michael House and Joel Gummer and Robert Trengove and John Olynyk and Darrell Crawford and Leon Adams",

year = "2018",

month = jun,

doi = "10.1002/hep4.1190",

language = "English",

volume = "2",

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journal = "Hepatology communications",

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Britton, L, Bridle, K, Reiling, J, Santrampurwala, N, Wockner, L, Ching, H, Stuart, K, Subramaniam, VN, Jeffrey, G, St Pierre, T, House, M, Gummer, J, Trengove, R, Olynyk, J, Crawford, D & Adams, L 2018, 'Hepatic Iron Concentration Correlates With Insulin Sensitivity in Nonalcoholic Fatty Liver Disease', Hepatology communications, vol. 2, no. 6, pp. 644-653. https://doi.org/10.1002/hep4.1190

TY - JOUR

T1 - Hepatic Iron Concentration Correlates With Insulin Sensitivity in Nonalcoholic Fatty Liver Disease

AU - Britton, Laurence

AU - Bridle, Kim

AU - Reiling, Janske

AU - Santrampurwala, Nishreen

AU - Wockner, Leesa

AU - Ching, Helena

AU - Stuart, Katherine

AU - Subramaniam, V. Nathan

AU - Jeffrey, Gary

AU - St Pierre, Tim

AU - House, Michael

AU - Gummer, Joel

AU - Trengove, Robert

AU - Olynyk, John

AU - Crawford, Darrell

AU - Adams, Leon

PY - 2018/6

Y1 - 2018/6

N2 - 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 alpha, and interleukin6, using a Qiantibody, 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 Alc, 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.

AB - 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 alpha, and interleukin6, using a Qiantibody, 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 Alc, 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.

KW - ADIPOSE-TISSUE

KW - RESISTANCE

KW - ADIPONECTIN

KW - METABOLISM

KW - OVERLOAD

KW - OBESITY

KW - HEMOCHROMATOSIS

KW - EXPRESSION

KW - HEPCIDIN

KW - GLUCOSE

U2 - 10.1002/hep4.1190

DO - 10.1002/hep4.1190

M3 - Article

C2 - 29881816

SN - 2471-254X

VL - 2

SP - 644

EP - 653

JO - Hepatology communications

JF - Hepatology communications

IS - 6

ER -