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...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/7281986 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lakshini Weerasekera |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-b2f0e0939cee45968bc44b212bf4f2f2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b2f0e0939cee45968bc44b212bf4f2f22025-02-03T01:31:28ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/72819867281986ADAM19: A Novel Target for Metabolic Syndrome in Humans and MiceLakshini Weerasekera0Caroline Rudnicka1Qing-Xiang Sang2Joanne E. Curran3Matthew P. Johnson4Eric K. Moses5Harald H. H. Göring6John Blangero7Jana Hricova8Markus Schlaich9Vance B. Matthews10School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, AustraliaRoyal Perth Hospital, Perth, AustraliaDepartment of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USASouth Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USASouth Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USACentre 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, AustraliaSouth Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USASouth Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USASchool of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, AustraliaSchool of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, AustraliaSchool of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, AustraliaObesity 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.http://dx.doi.org/10.1155/2017/7281986 |
| spellingShingle | 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 ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice Mediators of Inflammation |
| 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://dx.doi.org/10.1155/2017/7281986 |
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