Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis

Steven Alfred Bloomer, Alicia K. Olivier, Ottar M. Bergmann, M. Meleah Mathahs, Kimberly A. Broadhurst, Hasan Hicsasmaz, Kyle E. Brown

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Nonalcoholic steatohepatitis is a common liver disease that is often accompanied by dysregulated iron metabolism. The aim of the study was to test the hypothesis that aberrant iron metabolism in nonalcoholic steatohepatitis is modulated by genetic susceptibility to inflammation and oxidative stress. Hepatic histology and iron content were assessed in 3 inbred strains of mice (C57BL/6, BALB/c, and C3H/HeJ) fed an atherogenic diet (AD). Hepatic expression of genes relevant to iron metabolism, inflammation, and oxidative stress were quantitated by real-time reverse transcription-polymerase chain reaction. At 6 weeks on the AD, histologic injury and induction of inflammatory and oxidative stress-associated gene expression were most pronounced in C57BL/6. At 18 weeks on the AD, these parameters were similar in C57BL/6 and BALB/c. Atherogenic diet–fed C3H/HeJ showed milder responses at both time points. The AD was associated with decreased hepatic iron concentrations in all strains at 6 and 18 weeks. The decrease in hepatic iron concentrations did not correlate with changes in hepcidin expression and was not associated with altered expression of iron transporters. These findings are similar to those observed in models of obesity-induced steatosis and indicate that hepatic steatosis can be associated with depletion of iron stores that is not explained by upregulation of hepcidin expression by inflammation. Significance of the study: Nonalcoholic steatohepatitis (NASH) is a common liver disease that often accompanies the metabolic syndrome. The latter condition has been linked to iron deficiency and diminished intestinal iron absorption, likely the result of hepcidin upregulation by chronic inflammation. Paradoxically, some NASH patients accumulate excess hepatic iron, which may increase fibrosis and cancer risk. Iron accumulation has been attributed to suppression of hepcidin by oxidative stress. The objective of this study was to investigate the contributions of inflammation and oxidative stress to altered hepatic iron metabolism in a murine model of NASH using inbred strains of mice with differing susceptibilities to injury.

Original languageEnglish (US)
Pages (from-to)628-639
Number of pages12
JournalCell Biochemistry and Function
Volume34
Issue number8
DOIs
StatePublished - Dec 1 2016

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Metabolism
Iron
Liver
Oxidative stress
Atherogenic Diet
Hepcidins
Nutrition
Oxidative Stress
Inflammation
Inbred Strains Mice
Non-alcoholic Fatty Liver Disease
Liver Diseases
Up-Regulation
Gene Expression
Histology
Polymerase chain reaction
Intestinal Absorption
Wounds and Injuries
Transcription
Genetic Predisposition to Disease

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Bloomer, S. A., Olivier, A. K., Bergmann, O. M., Mathahs, M. M., Broadhurst, K. A., Hicsasmaz, H., & Brown, K. E. (2016). Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis. Cell Biochemistry and Function, 34(8), 628-639. https://doi.org/10.1002/cbf.3238
Bloomer, Steven Alfred ; Olivier, Alicia K. ; Bergmann, Ottar M. ; Mathahs, M. Meleah ; Broadhurst, Kimberly A. ; Hicsasmaz, Hasan ; Brown, Kyle E. / Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis. In: Cell Biochemistry and Function. 2016 ; Vol. 34, No. 8. pp. 628-639.
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Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis. / Bloomer, Steven Alfred; Olivier, Alicia K.; Bergmann, Ottar M.; Mathahs, M. Meleah; Broadhurst, Kimberly A.; Hicsasmaz, Hasan; Brown, Kyle E.

In: Cell Biochemistry and Function, Vol. 34, No. 8, 01.12.2016, p. 628-639.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis

AU - Bloomer, Steven Alfred

AU - Olivier, Alicia K.

AU - Bergmann, Ottar M.

AU - Mathahs, M. Meleah

AU - Broadhurst, Kimberly A.

AU - Hicsasmaz, Hasan

AU - Brown, Kyle E.

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