Date Published: February 13, 2018
Publisher: Public Library of Science
Author(s): Arti Ahluwalia, Alessandra Misto, Federico Vozzi, Chiara Magliaro, Giorgio Mattei, Maria Cristina Marescotti, Angelo Avogaro, Elisabetta Iori, Christina Chan.
Metabolic disorders due to over-nutrition are a major global health problem, often associated with obesity and related morbidities. Obesity is peculiar to humans, as it is associated with lifestyle and diet, and so difficult to reproduce in animal models. Here we describe a model of human central adiposity based on a 3-tissue system consisting of a series of interconnected fluidic modules. Given the causal link between obesity and systemic inflammation, we focused primarily on pro-inflammatory markers, examining the similarities and differences between the 3-tissue model and evidence from human studies in the literature. When challenged with high levels of adiposity, the in-vitro system manifests cardiovascular stress through expression of E-selectin and von Willebrand factor as well as systemic inflammation (expressing IL-6 and MCP-1) as observed in humans. Interestingly, most of the responses are dependent on the synergic interaction between adiposity and the presence of multiple tissue types. The set-up has the potential to reduce animal experiments in obesity research and may help unravel specific cellular mechanisms which underlie tissue response to nutritional overload.
Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes , cardiovascular diseases and cancer . Since the turn of the century, the number of obese adults has increased to over 300 million. Obese individuals often have excess central visceral adiposity, a condition that contributes to a chronic increase in circulating free fatty acids and metabolites, such as glycerol and triglycerides. These metabolites in turn activate various signaling cascades that interfere with insulin signaling and β-cell function, further contributing to gluco/lipotoxicity .
Hepatocytes seeded on 3D porous collagen scaffolds, endothelial cells and adipose tissue were cultured together in a fluidic system. Keeping the hepatic and endothelial compartments constant, the quantity of adipose tissue (AT) was varied to represent central or visceral obesity (35%AT), overweight (25%AT) and normo-weight (12%AT) respectively. Our aim was to investigate the interactions among the three tissues as a function of the percentage of adipose tissue as a first step towards the development of a non-animal model for studying the effects of obesity in humans. Given the association between adiposity and hyperlipidemia as well as the causal link between obesity and systemic inflammation , we focused primarily on lipid-related molecules and pro-inflammatory markers, examining the similarities and differences between the 3-way model and evidence from human studies in the literature.