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ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318628/ https://www.ncbi.nlm.nih.gov/pubmed/28265178 http://dx.doi.org/10.1155/2017/7281986 |
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author | 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. |
author_facet | 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. |
author_sort | Weerasekera, Lakshini |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5318628 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-53186282017-03-06 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. Mediators Inflamm Research Article 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. Hindawi Publishing Corporation 2017 2017-02-07 /pmc/articles/PMC5318628/ /pubmed/28265178 http://dx.doi.org/10.1155/2017/7281986 Text en Copyright © 2017 Lakshini Weerasekera et al. https://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Research Article 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 |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318628/ https://www.ncbi.nlm.nih.gov/pubmed/28265178 http://dx.doi.org/10.1155/2017/7281986 |
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