Vascular Damage in Obesity and Diabetes: Highlighting Links Between Endothelial Dysfunction and Metabolic Disease in Zebrafish and Man

Abstract

Endothelial dysfunction is an initial pathophysiological mechanism of vascular damage and is further recognized as an independent predictor of negative prognosis in diabetes-induced micro- and macrovascular complications. Insight into the capability of zebrafish to model metabolic disease like obesity and type II diabetes has increased and new evidence on the induction of vascular pathologies in zebrafish through metabolic disease is available. Here, we raise the question, if zebrafish can be utilized to study the initial impairments of vascular complications in metabolic disorders. In this review, we focus on the advances made to develop models of obesity and type II diabetes in zebrafish, discuss the key points and characteristics of these models, while highlighting the available information linked to the development of endothelial dysfunction in zebrafish and man. We show that larval and adult zebrafish develop metabolic dysregulation in the settings of obesity and diabetes, exhibiting pathophysiological mechanisms, which mimic the human condition. The most important genes related to endothelial dysfunction are present in zebrafish and further display similar functions as in mammals. Several suggested contributors to endothelial dysfunction found in these models, namely hyperinsulinaemia, hyperglycaemia, hyperlipidaemia and hyperleptinaemia are highlighted and the available data from zebrafish are summarised. Many underlying processes of endothelial dysfunction in obesity and diabetes are fundamentally present in zebrafish and provide ground for the assumption, that zebrafish can develop endothelial dysfunction. Conservation of basic biological mechanisms is established for zebrafish, but focused investigation on the subject is now needed as validation and particularly more research is necessary to understand the differences between zebrafish and man. The available data demonstrate the relevance of zebrafish as a model for metabolic disease and their ability to become a proponent for the investigation of vascular damage in the settings of obesity and diabetes.

Keywords: Endothelial function; danio rerio; diabetes mellitus; endothelial dysfunction; macrovascular complications; microvascular complications; obesity; zebrafish..