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Title: ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice.
Name(s): Weerasekera, Lakshini, author
Rudnicka, Caroline, author
Sang, Qing-Xiang, author
Curran, Joanne E, author
Johnson, Matthew P, author
Moses, Eric K, author
Göring, Harald H H, author
Blangero, John, author
Hricova, Jana, author
Schlaich, Markus, author
Matthews, Vance B, author
Type of Resource: text
Genre: Journal Article
Date Issued: 2017-01-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/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- 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.
Identifier: FSU_pmch_28265178 (IID), 10.1155/2017/7281986 (DOI), PMC5318628 (PMCID), 28265178 (RID), 28265178 (EID)
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at
Subject(s): ADAM Proteins/antagonists & inhibitors
ADAM Proteins/genetics
ADAM Proteins/metabolism
Diet, High-Fat/adverse effects
Insulin Resistance/immunology
Insulin Resistance/physiology
Leukocytes, Mononuclear/metabolism
Metabolic Syndrome/immunology
Metabolic Syndrome/metabolism
Metabolic Syndrome/pathology
Mice, Inbred C57BL
RNA, Small Interfering
Tumor Necrosis Factor-alpha/metabolism
Persistent Link to This Record:
Host Institution: FSU
Is Part Of: Mediators of inflammation.
Issue: vol. 2017

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Weerasekera, L., Rudnicka, C., Sang, Q. -X., Curran, J. E., Johnson, M. P., Moses, E. K., … Matthews, V. B. (2017). ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice. Mediators Of Inflammation. Retrieved from