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

© 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 Meta...

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Main Authors: Weerasekera, L., Rudnicka, C., Sang, Q., Curran, J., Johnson, M., Moses, Eric, Göring, H., Blangero, J., Hricova, J., Schlaich, M., Matthews, V.
Format: Journal Article
Published: Hindawi Publishing Corporation 2017
Online Access:http://hdl.handle.net/20.500.11937/61844
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author Weerasekera, L.
Rudnicka, C.
Sang, Q.
Curran, J.
Johnson, M.
Moses, Eric
Göring, H.
Blangero, J.
Hricova, J.
Schlaich, M.
Matthews, V.
author_facet Weerasekera, L.
Rudnicka, C.
Sang, Q.
Curran, J.
Johnson, M.
Moses, Eric
Göring, H.
Blangero, J.
Hricova, J.
Schlaich, M.
Matthews, V.
author_sort Weerasekera, L.
building Curtin Institutional Repository
collection Online Access
description © 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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institution Curtin University Malaysia
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publishDate 2017
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spelling curtin-20.500.11937-618442018-02-01T05:55:53Z ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice Weerasekera, L. Rudnicka, C. Sang, Q. Curran, J. Johnson, M. Moses, Eric Göring, H. Blangero, J. Hricova, J. Schlaich, M. Matthews, V. © 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/61844 10.1155/2017/7281986 Hindawi Publishing Corporation unknown
spellingShingle Weerasekera, L.
Rudnicka, C.
Sang, Q.
Curran, J.
Johnson, M.
Moses, Eric
Göring, H.
Blangero, J.
Hricova, J.
Schlaich, M.
Matthews, V.
ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
title ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
title_full ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
title_fullStr ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
title_full_unstemmed ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
title_short ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
title_sort adam19: a novel target for metabolic syndrome in humans and mice
url http://hdl.handle.net/20.500.11937/61844