Impact of multiple stressors on adipose tissue using precision-cut adipose tissue slices from pig and northern elephant seal

Details

Supervisors

Debier, Cathy ; Pirard, Laura

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries, à finalité spécialisée

Abstract

Adipose tissue serves as a vital endocrine organ, playing crucial roles in numerous biological functions and contributing significantly to metabolic homeostasis. This organ is also susceptible to the effects of persistent organic pollutants (POPs) due to their lipophilic properties. The presence of these pollutants, along with other natural and anthropogenic stressors, can profoundly disrupt the development and function of adipose tissue, leading to severe health issues and reproductive problems in both human and wild animal populations, including marine mammals. Understanding the interactive effects of multiple stress factors on adipose tissue function is crucial. The objective of this master's thesis was to investigate the individual and combined impacts of various stressors on adipose tissue, using a porcine model to represent human health and the northern elephant seal (NES) as a marine mammal model. To achieve this objective, we used an ex-vivo approach of precision-cut adipose tissue slices (PCATS). PCATS were exposed to DDE alone as well as to a relevant mixture of Aroclor 1254, BDE-47, BDE-99, and DDE (referred to as the POP mixture), which reflects contaminant levels found in both human and marine mammalian adipose tissue. Our investigation on pig PCATS focused on assessing the metabolic functions of adipose tissue in the presence of POPs at two concentrations. To evaluate the dynamics of lipolysis, we measured the release of lipolysis products, glycerol and free fatty acids, from pig PCATS, as well as the expression of key lipolytic genes. The lower concentrations of DDE and the mixture of POPs decreased the release of the lipolytic products in basal and epinephrine-induced lipolysis. This decrease in lipolysis exhibited a dose-dependent relationship, as no impact was observed with the higher concentration of POPs. Although no significant differences in gene expression were detected at the lowest concentrations of DDE or the POPs mix, there were non-significant trends towards a decrease in the expression levels of two genes, namely β2-adrenergic receptor (β2-AR) and comparative gene identification-58 (CGI-58). Regarding the experiments conducted on NES PCATS, our aim was to examine the individual and combined effects of stress hormones (epinephrine and cortisol), POPs (a mixture of DDE, Aroclor 1254, and PBDEs), and high hydrostatic pressures (ranging from 1 to 30 bar) on the lipid composition of PCATS. Specifically, we investigated the fatty acid profile of two major lipid fractions in adipose tissue: neutral lipids and phospholipids. Our analysis of lipid profiles in lipid droplets revealed that the combination of multiple stress factors had a significant impact on the levels of several fatty acids, mainly n-6 polyunsaturated fatty acids. However, no impact was observed on the fatty acid profiles of membranes. These results provide further evidence of the influence of multiple stress factors on this crucial organ of the endocrine system. Future studies should be conducted to elucidate and complement these promising findings.