Systemic and vascular inflammation in an in-vitro model of central obesity

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.

Neutrophil‐to‐lymphocyte ratio and its relation with pro‐inflammatory mediators, visceral adiposity and carotid intima‐media thickness in population with obesity

“…Neutrophil‐to‐lymphocyte ratio represents a rapidly accessible and inexpensive marker derived from values of a routine hemogram, which has shown to correlate with systemic inflammation in critical ill patients, chronic low‐grade inflammation, accumulation of lipids in the vascular wall and atherogenic mechanisms …”

Invited review: Dairy proteins and bioactive peptides: Modeling digestion and the intestinal barrier

“…A strict interaction among the gut epithelium, microbiota, and the secondary target tissues exists due to chemical and biological signals mediated by food compounds or their metabolites. The application of multiorgan cell culture models composed of a series of bioreactors simulating the dynamics of the different tissue environment in a single model was proposed by Ahluwalia et al (2018). Each bioreactor contains a specific cell type and all bioreactors are interconnected by a continual flux of culture medium.…”

Scleroderma-specific autoantibodies embedded in immune complexes mediate endothelial damage: an early event in the pathogenesis of systemic sclerosis

“…Such partial insight into disease etiopathogenesis provides one of the limitations that flaw our study. To overcome this critical issue, we are implementing a dynamic in vitro model that envisages multiple bioreactors for 3D cell cultures interconnected by a dynamic flow in order to mimic the cell crosstalk that characterizes SSc pathogenesis in humans [ 50 ]. Another major limitation of this study relates to the scarce number of samples for each autoantibody specificity; unfortunately, the recruitment of a broader cohort of patients is prevented by the relative rarity of certain antibodies (e.g., ARA and anti-Th/To) in the Italian SSc population [ 51 ].…”