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

Authors

Lakshini Weerasekera
Caroline Rudnicka
Qing-Xiang Sang
Joanne E. Curran, The University of Texas Rio Grande Valley
Matthew P. Johnson, The University of Texas Rio Grande Valley
Eric K. Moses
Harald H. H. Goring, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
Jana Hricova
Markus Schlaich
Vance B. Matthews

Document Type

Article

Publication Date

2-7-2017

Abstract

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.

Comments

©2017 Lakshini Weerasekera et al.

Recommended Citation

Weerasekera, L., Rudnicka, C., Sang, Q.-X., Curran, J. E., Johnson, M. P., Moses, E. K., Göring, H. H. H., Blangero, J., Hricova, J., Schlaich, M., & Matthews, V. B. (2017). ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice. Mediators of Inflammation, 2017, 7281986. https://doi.org/10.1155/2017/7281986

Publication Title

Mediators of Inflammation

DOI

10.1155/2017/7281986

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics