TY - JOUR
T1 - Ferroportin Expression in Adipocytes Does Not Contribute to Iron Homeostasis or Metabolic Responses to a High Calorie Diet
AU - Britton, Laurence
AU - Jaskowski, Lesley-Anne
AU - Bridle, Kim
AU - Secondes, Eriza
AU - Wallace, Daniel
AU - Santrampurwala, Nishreen
AU - Reiling, Janske
AU - Miller, Gregory
AU - Mangiafico, Salvatore
AU - Andrikopoulos, Sofianos
AU - Subramaniam, V. Nathan
AU - Crawford, Darrell
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Iron
KW - Ferroportin
KW - Adipose Tissue
KW - Nonalcoholic Fatty Liver Disease
KW - FATTY LIVER-DISEASE
KW - ADIPOSE-TISSUE
KW - INSULIN-RESISTANCE
KW - NONALCOHOLIC STEATOHEPATITIS
KW - OBESITY
KW - HEPCIDIN
KW - OVERLOAD
KW - MICE
KW - ADIPONECTIN
KW - DEFICIENCY
U2 - 10.1016/j.jcmgh.2018.01.005
DO - 10.1016/j.jcmgh.2018.01.005
M3 - Article
C2 - 29552621
SN - 2352-345X
VL - 5
SP - 319
EP - 331
JO - Cellular and molecular gastroenterology and hepatology
JF - Cellular and molecular gastroenterology and hepatology
IS - 3
ER -