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Mediators of Inflammation
Volume 2017, Article ID 7281986, 9 pages
Research Article

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

1School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
2Royal Perth Hospital, Perth, Australia
3Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA
4South Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA
5Centre for Genetic Origins of Health & Diseases, Faculty of Medicine, Dentistry & Health Sciences, University of Western Australia and Faculty of Health Sciences, Curtin University, Western Australia, Australia

Correspondence should be addressed to Vance B. Matthews; ua.ude.awu@swehttam.ecnav

Received 13 October 2016; Accepted 12 January 2017; Published 7 February 2017

Academic Editor: Julio Galvez

Copyright © 2017 Lakshini Weerasekera et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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-α 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-α 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.