Baily, Thomas
[UCL]
Debier, Cathy
[UCL]
Rees, Jean-François
[UCL]
Long considered as a simple storage site for energy excess, adipose tissue (AT) is in fact an essential endocrine organ that interacts with the whole body. Nowadays, there is growing epidemiological, in vivo and in vitro evidence that the disruption of AT development and function by persistent organic pollutants (POPs) as well as by physiological stress situations can lead to serious health problems such as type 2 diabetes and obesity. However, some of the underlying mechanisms remain unclear and the possible interaction between stress hormones and POPs has never been studied to date. In that context, the aim of this master thesis was to determine the impact of stressors (stress hormones -epinephrine and cortisol- and POPs -PCBs, PBDEs and DDE-), individually and in combination, on porcine precision-cut adipose tissue slices (PCATS) as an in vitro model for human health. Prior to any experiment, a relevant mixture of POPs (POPs Mix) containing Aroclor1254, BDE-47, BDE-99 and DDE was developed. The pollutants proportions and concentrations used in our experiments were determined by compiling studies on the levels of these contaminants found in human AT and serum. Then, we investigated the impact of the stress hormones and POPs on PCATS i) viability (LDH release), ii) functionality via lipolysis (glycerol release as well as gene expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), two key lipolytic enzymes) and iii) inflammation (gene expression of tumor necrosis factor α (TNFα), a proinflammatory cytokine). We showed that epinephrine induced lipolysis from a concentration of 1 µM. Cortisol (2 µM) itself did not induce lipolysis and did not potentiate the lipolytic effect of epinephrine. We also observed that, at 0.1 µM, DDE alone downregulated basal lipolysis while the POPs Mix (containing 0.1 µM DDE) downregulated both basal and induced lipolysis. Interestingly, no impact was observed with a DDE concentration of 1 µM (alone or in the POPs Mix). ATGL gene expression analysis did not give significant results despite the large fold changes observed. HSL gene expression could not be analysed due to an optimisation problem. Regarding TNFα gene expression, our results were highly variable and did not allow to provide evidence on the impacts of epinephrine and POPs on inflammation. This high variability was probably due to the low level of TNFα gene expression in the PCATS. It is worth noticing that, at the concentrations used, no stressor had a cytotoxic effect. By showing that DDE alone or in a POPs mixture representative of the human burden impairs AT function, we provided further evidence of the impact of these stressors on a major organ of the endocrine system. In the near future as well as in the longer term, further investigations should be conducted to explain and complement our promising results.
Bibliographic reference |
Baily, Thomas. Impact of stress hormones and persistent organic pollutants on adipose tissue using precision-cut adipose tissue slices from pig. Faculté des bioingénieurs, Université catholique de Louvain, 2022. Prom. : Debier, Cathy ; Rees, Jean-François. |
Permanent URL |
http://hdl.handle.net/2078.1/thesis:38155 |