Interplay of adipocyte and hepatocyte: Leptin upregulates hepcidin
- Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, 663-8501 (Japan)
Highlights: • Plasma levels of hepcidin in ob/ob mice is significantly higher than those of control mice. • Leptin administration to ob/ob mice significantly increase in plasma and liver expression of Hanmp mRNA and iron content in the liver. • As well as the expression of Hanmp mRNA, hepcidin related genes (BMP6 mRNA, STAT3 mRNA) and iron transporters (DMT1 mRNA, TfR mRNA) in the liver also increased after administration of leptin to ob/ob mice. Conflicting evidence concerning leptin, an adipocyte-derived hormone, in atherogenesis and non-alcoholic fatty liver disease (NAFLD) has been reported. Iron metabolism and iron-mediated oxidative stress should be taken into consideration for the clarification of the pathogenesis of these diseases. In this study, we demonstrate that leptin receptor activation directly affects iron metabolism by the finding that serum levels of hepcidin, the master regulator of iron in the whole body, were significantly lower in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. The administration of recombinant leptin to ob/ob mice for two weeks showed a significant increase in serum hepcidin and hepatic Hamp mRNA levels. Hamp mRNA levels were significantly correlated with hepatic iron content and BMP6 mRNA levels. Hepatic iron content was associated with the increase in mRNA levels of divalent metal transporter 1 and transferrin receptor. Our data provide evidence that the interplay of these two hormones could help improve the understanding of the pathogenesis of atherosclerosis and NAFLD.
- OSTI ID:
- 23134416
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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