title: ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice.
abstract: 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-αlevels. 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-αlevels. 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.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Lakshini
authors.initials: L
authors.lastname: Weerasekera
authors.affiliation: Royal Perth Hospital, Perth, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rudnicka
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA.
authors.forename: Qing-Xiang
authors.initials: QX
authors.lastname: Sang
authors.affiliation: South Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: Joanne E
authors.identifier: 0000-0002-6898-155X
authors.initials: JE
authors.lastname: Curran
authors.affiliation: South Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: Centre 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, Australia.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.affiliation: South Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.affiliation: South Texas Diabetes & Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Jana
authors.initials: J
authors.lastname: Hricova
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia; Royal Perth Hospital, Perth, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Schlaich
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Vance B
authors.identifier: 0000-0003-3955-3692
authors.initials: VB
authors.lastname: Matthews
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; C411902:ADAM19 protein, human; C096116:Adam19 protein, mouse