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    ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice

    Access Status
    Open access via publisher
    Authors
    Weerasekera, L.
    Rudnicka, C.
    Sang, Q.
    Curran, J.
    Johnson, M.
    Moses, Eric
    Göring, H.
    Blangero, J.
    Hricova, J.
    Schlaich, M.
    Matthews, V.
    Date
    2017
    Type
    Journal Article
    
    Metadata
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    Citation
    Weerasekera, L. and Rudnicka, C. and Sang, Q. and Curran, J. and Johnson, M. and Moses, E. and Göring, H. et al. 2017. ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice. Mediators of Inflammation. 2017.
    Source Title
    Mediators of Inflammation
    DOI
    10.1155/2017/7281986
    ISSN
    0962-9351
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/61844
    Collection
    • Curtin Research Publications
    Abstract

    © 2017 Lakshini Weerasekera et al. Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with insulin resistance, which may ultimately culminate in type 2 diabetes (T2D). We sought to ascertain whether the human metalloproteinase A Disintegrin and Metalloproteinase 19 (ADAM19) correlates with parameters of the metabolic syndrome in humans and mice. To determine the potential novel role of ADAM19 in the metabolic syndrome, we first conducted microarray studies on peripheral blood mononuclear cells from a well-characterised human cohort. Secondly, we examined the expression of ADAM19 in liver and gonadal white adipose tissue using an in vivo diet induced obesity mouse model. Finally, we investigated the effect of neutralising ADAM19 on diet induced weight gain, insulin resistance in vivo, and liver TNF-levels. Significantly, we show that, in humans, ADAM19 strongly correlates with parameters of the metabolic syndrome, particularly BMI, relative fat, HOMA-IR, and triglycerides. Furthermore, we identified that ADAM19 expression was markedly increased in the liver and gonadal white adipose tissue of obese and T2D mice. Excitingly, we demonstrate in our diet induced obesity mouse model that neutralising ADAM19 therapy results in weight loss, improves insulin sensitivity, and reduces liver TNF-levels. Our novel data suggest that ADAM19 is pro-obesogenic and enhances insulin resistance. Therefore, neutralisation of ADAM19 may be a potential therapeutic approach to treat obesity and T2D.

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