Endocrine disrupting compounds and adipose tissue

Details

Supervisors

Debier, Cathy

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences pharmaceutiques

Abstract

Obesity is a widespread disease that affects more than 1.9 billion adults. Its pathophysiology has been reduced to excessive calorie intake coupled with a lack of physical activity. However, these two causes are not enough to explain all cases of obesity. Among the other mechanisms mentioned, the action of endocrine disruptors is one of the major hypotheses put forward. The aim of this thesis is to review the scientific literature on the links between endocrine disruptors on the one hand and changes in adipose tissue and obesity on the other. The physiology of adipose tissue is complex and can be disrupted at different stages of adipogenesis, lipogenesis or even lipolysis under the effect of endocrine disruptors. The main endocrine disruptors incriminated in the literature for their role on adipose tissue are bisphenol A (BPA), phthalates (DEHP, MEHP) and dichlorodiphenyltrichloroethane (DDT). Studies show that BPA is involved in the activation of the central regulator of adipogenesis PPAR. This activation can increase adipogenesis and lipid storage leading to increased number and size of adipocytes. DEHP has also been shown to act on the Janus kinase 3 (JAK 3) and Activators of Transcription (STAT 5) signal transcription pathway. Its metabolite MEHP, for its part, acts through the TYK-STAT3 pathway on adipocytes. Other studies show the toxic action of DDT and its metabolite DDE on the mitochondria which results in the formation of "reactive oxygen species" (ros). Ros will deregulate adipogenesis and participate in the inflammatory phenomena of obesity. However, there are limits to the interpretation of these results as, for instance, these studies most often only relate to a single compound used at doses different from those encountered in a real-life situation. Studies on the effects of simultaneous exposure to several endocrine disruptors and at the doses usually encountered are necessary to conclude on the impact of endocrine disruptors on adipose tissue changes and obesity.