Abstract
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.
Highlights
Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes [1], cardiovascular diseases and cancer [2]
The effect of both adiposity (i.e. 12, 25 and 35%AT) and model complexity (i.e. 1, 2- and 3-way) on the production of triglycerides (TRG), glycerol (GLY), free fatty acids (FFAs) and albumin (HA) after 24 h of culture was investigated in order to determine whether and how lipids and lipidrelated metabolite levels in the system are modulated by the amount of adipose tissue considered in the model and/or by cross-talk between multiple tissues
We observed a net release of FFAs in the 3-way media over 24 hours (Fig 2c), the levels were very similar independent of the percentage of adipose tissue added to the system
Summary
Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes [1], cardiovascular diseases and cancer [2]. 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 Ī²-cell function, further contributing to gluco/lipotoxicity [3]. As succinctly put by Wang et al, ādespite the extensive use of these rodent models, many mechanistic details of human metabolism remain poorly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
