Original Research
Ferroportin Expression in Adipocytes Does Not Contribute to Iron Homeostasis or Metabolic Responses to a High Calorie Diet

https://doi.org/10.1016/j.jcmgh.2018.01.005Get rights and content
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Background & Aims

Iron has an increasingly recognized role in the regulation of adipose tissue function, including the expression of adipokines involved in the pathogenesis of nonalcoholic fatty liver disease. The cellular iron exporter, ferroportin, has been proposed as being a key determinant of adipocyte iron homeostasis.

Methods

We studied an adipocyte-specific ferroportin (Fpn1) knockout mouse model, using an Adipoq-Cre recombinase driven Fpn1 deletion and fed mice according to the fast food diet model of nonalcoholic steatohepatitis.

Results

We showed successful selective deletion of Fpn1 in adipocytes, but found that this did not lead to increased adipocyte iron stores as measured by atomic absorption spectroscopy or histologically quantified iron granules after staining with 3,3’-diaminobenzidine–enhanced Perls’ stain. Mice with adipocyte-specific Fpn1 deletion did not show dysregulation of adiponectin, leptin, resistin, or retinol-binding protein-4 expression. Similarly, adipocyte-specific Fpn1 deletion did not affect insulin sensitivity during hyperinsulinemic–euglycemic clamp studies or lead to histologic evidence of increased liver injury. We have shown, however, that the fast food diet model of nonalcoholic steatohepatitis generates an increase in adipose tissue macrophage infiltration with crown-like structures, as seen in human beings, further validating the utility of this model.

Conclusions

Ferroportin may not be a key determinant of adipocyte iron homeostasis in this knockout model. Further studies are needed to determine the mechanisms of iron metabolism in adipocytes and adipose tissue.

Keywords

Iron
Ferroportin
Adipose Tissue
Nonalcoholic Fatty Liver Disease

Abbreviations used in this paper

AAS
atomic absorption spectroscopy
Adipoq
adiponectin
ANOVA
analysis of variance
AUC
area under the curve
bp
base pair
cDNA
complementary DNA
EFP
epididymal fat pad
FKO
ferroportin knockout
Ferroportin Flox
Fpn1fl/fl
Fpn1
ferroportin
Hamp1
hepcidin
HIC
hepatic iron concentration
mRNA
messenger RNA
NAFLD
nonalcoholic fatty liver disease
NASH
nonalcoholic steatohepatitis
PCR
polymerase chain reaction
RBP-4
retinol binding protein-4
Tfr1
transferrin receptor-1

Cited by (0)

Author contributions Laurence Britton was responsible for the study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and statistical analysis; Lesley-Anne Jaskowski was responsible for the acquisition of data, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and technical support; Kim Bridle was responsible for the study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and study supervision; Eriza Secondes was responsible for the acquisition of data and technical support; Daniel Wallace was responsible for the study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content; Nishreen Santrampurwala was responsible for the study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content; Janske Reiling was responsible for the study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content; Gregory Miller was responsible for the analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content; Salvatore Mangiafico was responsible for the study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content; Sofianos Andrikopoulos was responsible for the study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and material support; V. Nathan Subramaniam was responsible for the study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, material support, and study supervision; and Darrell Crawford was responsible for the study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, statistical analysis, material support, and study supervision.

Conflicts of interest The authors disclose no conflicts.

Funding Supported by funding from the National Health and Medical Research Council (APP1029574); and by scholarships from the Gallipoli Medical Research Foundation and the Gastroenterological Society of Australia (L.B.).

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Authors share co-senior authorship.