ADAM19: A Novel Target for Metabolic Syndrome in Humans and Mice
MetadataShow full item record
Â© 2017 Lakshini Weerasekera et al. 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.
Showing items related by title, author, creator and subject.
Shining LIGHT on the metabolic role of the cytokine TNFSF14 and the implications on hepatic IL-6 productionSaunders, B.; Rudnicka, C.; Filipovska, A.; Davies, S.; Ward, Natalie; Hricova, J.; Schlaich, M.; Matthews, V. (2018)The cytokine Tumor Necrosis Factor Superfamily member 14, TNFSF14 (or LIGHT), is a controversial player in numerous diseases. We investigated the role of endogenously expressed TNFSF14 in diet-induced obesity in vivo. ...
Newsholme, Philip; Cruzat, Vinicius; Arfuso, Frank; Keane, Kevin (2014)Pancreatic ß-cell function is of critical importance in the regulation of fuel homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus (DM). The ß-cell is an intricately designed cell type that couples ...
The bile acid membrane receptor TGR5: a novel pharmacological target in metabolic, inflammatory and neoplastic disordersStepanov, V.; Stankov, K.; Mikov, Momir (2013)TGR5 is the G-protein–coupled bile acid-activated receptor, found in many human and animal tissues. Considering different endocrine and paracrine functions of bile acids, the current review focuses on the role of TGR5 as ...