The metalloproteinase ADAM28 promotes metabolic dysfunction in mice

Lakshini Herat, Caroline Rudnicka, Yasunori Okada, Satsuki Mochizuki, Markus Schlaich, Vance Matthews

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28 mRNA and protein expression was markedly increased in the livers of mice with the metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the sympathetic nervous system, results in elevated Adam28 mRNA expression in human monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of weight gain, promotion of insulin sensitivity/glucose tolerance and decreased liver tumour necrosis factor-α (TNF-α) levels in our diet-induced obesity mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also displayed reduced body weight, elevated high density lipoprotein cholesterol levels, and reductions in blood urea nitrogen, alkaline phosphatase, and aspartate aminotransferase. The results of this study provide important insights into the pathogenic role of the metalloproteinase ADAM28 in the metabolic syndrome and suggests that downregulation of ADAM28 may be a potential therapeutic strategy in the metabolic syndrome.

    Original languageEnglish
    Article number884
    Number of pages12
    JournalInternational Journal of Molecular Sciences
    Volume18
    Issue number4
    DOIs
    Publication statusPublished - 21 Apr 2017

    Fingerprint

    obesity
    Disintegrins
    Metalloproteases
    mice
    aspartates
    pathogenesis
    diets
    phosphatases
    ureas
    liver
    blood
    sympathetic nervous system
    knockout mice
    monocytes
    Obesity
    lipoproteins
    neurotransmitters
    nitrogen
    body weight
    insulin

    Cite this

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    abstract = "Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28 mRNA and protein expression was markedly increased in the livers of mice with the metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the sympathetic nervous system, results in elevated Adam28 mRNA expression in human monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of weight gain, promotion of insulin sensitivity/glucose tolerance and decreased liver tumour necrosis factor-α (TNF-α) levels in our diet-induced obesity mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also displayed reduced body weight, elevated high density lipoprotein cholesterol levels, and reductions in blood urea nitrogen, alkaline phosphatase, and aspartate aminotransferase. The results of this study provide important insights into the pathogenic role of the metalloproteinase ADAM28 in the metabolic syndrome and suggests that downregulation of ADAM28 may be a potential therapeutic strategy in the metabolic syndrome.",
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    The metalloproteinase ADAM28 promotes metabolic dysfunction in mice. / Herat, Lakshini; Rudnicka, Caroline; Okada, Yasunori; Mochizuki, Satsuki; Schlaich, Markus; Matthews, Vance.

    In: International Journal of Molecular Sciences, Vol. 18, No. 4, 884, 21.04.2017.

    Research output: Contribution to journalArticle

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    AU - Herat, Lakshini

    AU - Rudnicka, Caroline

    AU - Okada, Yasunori

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