Matriptase-2 deficiency protects from obesity by modulating iron homeostasis

Alterations in iron status have frequently been associated with obesity and other metabolic disorders. The hormone hepcidin stands out as a key regulator in the maintenance of iron homeostasis by controlling the main iron exporter, ferroportin. Here we demonstrate that the deficiency in the hepcidin...

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Bibliographic Details
Published in:Nature communications 2018-04, Vol.9 (1), p.1350-12, Article 1350
Main Authors: Folgueras, Alicia R., Freitas-Rodríguez, Sandra, Ramsay, Andrew J., Garabaya, Cecilia, Rodríguez, Francisco, Velasco, Gloria, López-Otín, Carlos
Format: Article
Language:English
Subjects:
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Adipose tissue
Body fat
Control
Fatty liver
Glucose tolerance
Hepcidin
High fat diet
Homeostasis
Humanities and Social Sciences
Insulin
Iron
Lipolysis
Metabolic disorders
Mice
multidisciplinary
Obesity
Phenotypes
Rodents
Science
Science (multidisciplinary)
Steatosis
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Summary:Alterations in iron status have frequently been associated with obesity and other metabolic disorders. The hormone hepcidin stands out as a key regulator in the maintenance of iron homeostasis by controlling the main iron exporter, ferroportin. Here we demonstrate that the deficiency in the hepcidin repressor matriptase-2 (Tmprss6) protects from high-fat diet-induced obesity. Tmprss6 −/− mice show a significant decrease in body fat, improved glucose tolerance and insulin sensitivity, and are protected against hepatic steatosis. Moreover, these mice exhibit a significant increase in fat lipolysis, consistent with their dramatic reduction in adiposity. Rescue experiments that block hepcidin up-regulation and restore iron levels in Tmprss6 −/ − mice via anti-hemojuvelin (HJV) therapy, revert the obesity-resistant phenotype of Tmprss6 −/ − mice. Overall, this study describes a role for matritpase-2 and hepcidin in obesity and highlights the relevance of iron regulation in the control of adipose tissue function. Iron homeostasis dysfunctions have been associated with several metabolic disorders including obesity, steatosis and diabetes. Here the authors demonstrate that the hepcidin repressor matriptase-2 regulates adiposity and its deficiency protects mice against obesity and promotes lipolysis.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-03853-1