Next Article in Journal
A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine
Next Article in Special Issue
Matrix Metalloproteinase Gene Activation Resulting from Disordred Epigenetic Mechanisms in Rheumatoid Arthritis
Previous Article in Journal
Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats
Previous Article in Special Issue
Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and Response to Tumor Necrosis Factor (TNF) Inhibitors
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(4), 884; doi:10.3390/ijms18040884

The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice

1
Dobney Hypertension Centre, School of Medicine and Pharmacology, University of Western Australia, Crawley WA 6009, Australia
2
Research Centre, Royal Perth Hospital, Perth WA 6000, Australia
3
Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan
4
Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan
5
Department of Cardiology and Department of Nephrology, Royal Perth Hospital, Perth WA 6000, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Masatoshi Maki
Received: 17 February 2017 / Revised: 6 April 2017 / Accepted: 18 April 2017 / Published: 21 April 2017
(This article belongs to the Special Issue Metalloproteins 2017)
View Full-Text   |   Download PDF [2216 KB, uploaded 21 April 2017]   |  

Abstract

Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28 mRNA and protein expression was markedly increased in the livers of mice with the metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the sympathetic nervous system, results in elevated Adam28 mRNA expression in human monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of weight gain, promotion of insulin sensitivity/glucose tolerance and decreased liver tumour necrosis factor-α (TNF-α) levels in our diet-induced obesity mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also displayed reduced body weight, elevated high density lipoprotein cholesterol levels, and reductions in blood urea nitrogen, alkaline phosphatase, and aspartate aminotransferase. The results of this study provide important insights into the pathogenic role of the metalloproteinase ADAM28 in the metabolic syndrome and suggests that downregulation of ADAM28 may be a potential therapeutic strategy in the metabolic syndrome. View Full-Text
Keywords: ADAM28; type 2 diabetes (T2D); obesity; metabolic syndrome; metalloproteinases ADAM28; type 2 diabetes (T2D); obesity; metabolic syndrome; metalloproteinases
Figures

Figure 1

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. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Herat, L.; Rudnicka, C.; Okada, Y.; Mochizuki, S.; Schlaich, M.; Matthews, V. The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice. Int. J. Mol. Sci. 2017, 18, 884.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top