ADAM19: A novel target for metabolic syndrome in humans and mice

Lakshini Weerasekera, Caroline Rudnicka, Qing Xiang Sang, Joanne E. Curran, Matthew P. Johnson, Eric K. Moses, Harald H H Göring, John Blangero, Jana Hricova, Markus Schlaich, Vance B. Matthews

Research output: Contribution to journalArticle

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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. Copyright © 2017 Lakshini Weerasekera et al. 

Original languageEnglish
Article number7281986
Number of pages9
JournalMediators of Inflammation
Volume2017
DOIs
Publication statusPublished - 7 Feb 2017

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Disintegrins
Metalloproteases
Insulin Resistance
Obesity
Type 2 Diabetes Mellitus
White Adipose Tissue
Liver
Diet
Western World
Metabolic Diseases
Weight Gain
Weight Loss
Blood Cells
Triglycerides
Fats

Cite this

Weerasekera, Lakshini ; Rudnicka, Caroline ; Sang, Qing Xiang ; Curran, Joanne E. ; Johnson, Matthew P. ; Moses, Eric K. ; Göring, Harald H H ; Blangero, John ; Hricova, Jana ; Schlaich, Markus ; Matthews, Vance B. / ADAM19 : A novel target for metabolic syndrome in humans and mice. In: Mediators of Inflammation. 2017 ; Vol. 2017.
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Weerasekera, L, Rudnicka, C, Sang, QX, Curran, JE, Johnson, MP, Moses, EK, Göring, HHH, Blangero, J, Hricova, J, Schlaich, M & Matthews, VB 2017, 'ADAM19: A novel target for metabolic syndrome in humans and mice' Mediators of Inflammation, vol. 2017, 7281986. https://doi.org/10.1155/2017/7281986

ADAM19 : A novel target for metabolic syndrome in humans and mice. / Weerasekera, Lakshini; Rudnicka, Caroline; Sang, Qing Xiang; Curran, Joanne E.; Johnson, Matthew P.; Moses, Eric K.; Göring, Harald H H; Blangero, John; Hricova, Jana; Schlaich, Markus; Matthews, Vance B.

In: Mediators of Inflammation, Vol. 2017, 7281986, 07.02.2017.

Research output: Contribution to journalArticle

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AU - Johnson, Matthew P.

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Weerasekera L, Rudnicka C, Sang QX, Curran JE, Johnson MP, Moses EK et al. ADAM19: A novel target for metabolic syndrome in humans and mice. Mediators of Inflammation. 2017 Feb 7;2017. 7281986. https://doi.org/10.1155/2017/7281986