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

Laurence Britton*, Lesley-Anne Jaskowski, Kim Bridle, Eriza Secondes, Daniel Wallace, Nishreen Santrampurwala, Janske Reiling, Gregory Miller, Salvatore Mangiafico, Sofianos Andrikopoulos, V. Nathan Subramaniam, Darrell Crawford

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)319-331
Number of pages13
JournalCellular and molecular gastroenterology and hepatology
Volume5
Issue number3
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Iron
  • Ferroportin
  • Adipose Tissue
  • Nonalcoholic Fatty Liver Disease
  • FATTY LIVER-DISEASE
  • ADIPOSE-TISSUE
  • INSULIN-RESISTANCE
  • NONALCOHOLIC STEATOHEPATITIS
  • OBESITY
  • HEPCIDIN
  • OVERLOAD
  • MICE
  • ADIPONECTIN
  • DEFICIENCY

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