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

Arti Ahluwalia, Alessandra Misto, Federico Vozzi, Chiara Magliaro, Giorgio Mattei, Maria Cristina Marescotti, Angelo Avogaro, Elisabetta Iori

Journal: PloS one 2018;13(2):e0192824

PMID: 29438401

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Plain Language Summary

Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular disease and cancer. Obese individuals often have excess fat around the middle, known as central adiposity, a condition known to contribute to an increase in blood levels of compounds such as glycerol and triglycerides. This study builds on a series of studies in which it has been demonstrated that circulation of these compounds reduces glucose uptake and increases lactate availability in all cells. The aim of the study was to challenge the system in-vitro with increasing levels of adiposity to determine the impact this had on compounds in the blood and the extent to which this reflects obesity-related vascular and systemic stress observed in humans. The focus of the study was primarily on lipid-related molecules and pro-inflammatory markers. Visceral adipose tissue was obtained from 9 donors undergoing liver resection for metastatic/benign liver lesions without any underlying chronic liver disease or diabetic complications and body mass index ranging from 20-25. The study outlines that an increase of adiposity in-vitro determines a pro-inflammatory state and results in endothelial stress.

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.

Address: Research Center E. Piaggio, University of Pisa, Pisa, Italy.; Italian National Council of Research, Institute of Clinical Physiology, Pisa, Italy.; Department of Medicine, University of Padova, Padova, Italy.

DOI: 10.1371/journal.pone.0192824

Clinical Imbalances

Immune and inflammation Structural Integrity and Musculoskeletal

Modifiable Lifestyle Factors

Diet

Nutrition Evidence Keywords

Diabetes Bodymassindex BMI Obesity Obese Overweight Adiposity CardiovascularDisease Triglycerides Glucose Insulin Type2diabetes Metabolism Overnutrition Glucosehomeostasis FattyAcids Type1diabetes Energyhomeostasis Freefattyacids Metabolicprofile Adiposetissue Proinflammatorymarkers

Bioactive Substances

Triglycerides IL6 Eselectin Interleukin6 TNFalpha

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/vasculitis.html

Other Literature Sources:

https://scite.ai/reports/29438401

Miscellaneous:

https://assays.cancer.gov/CPTAC-327

MeSH Terms: Adiposity, Albumins, Animals, Biomarkers, Bioreactors, Coculture Techniques, Hep G2 Cells, Human Umbilical Vein Endothelial Cells, Humans, In Vitro Techniques, Inflammation, Inflammation Mediators, Intra-Abdominal Fat, Lab-On-A-Chip Devices, Lipids, Models, Biological, Obesity, Abdominal, Vasculitis