Phenolic compounds as modulators of leptin signalling pathway in peripheral tissues

Identifier:  TDX:2863

Handle: https://hdl.handle.net/20.500.11797/TDX2863

Authors:  Ardid Ruiz, Andrea

Abstract:
Obesity is a current and worldwide extended problem and one of the main factors related with other chronic pathologies. Conventional therapies, normally based on increasing the exercise and reducing the consumption of energy-dense food used to prevent or palliate obesity, are ineffective. In this sense, the use of bioactive compounds as polyphenols, a group of plant secondary metabolites with a wide range of beneficial healthy effects, arises as a novel strategy to combat obesity and its related pathologies. Leptin is a key hormone secreted proportionally by the amount of adipocytes that acts primarily in the central nervous system controlling the energy balance. In this process, leptin transport across the blood-brain barrier is especially important. In addition, leptin is implicated in the regulation of peripheral homeostasis, mainly modulating the lipid and carbohydrate metabolism, in organs such as liver, muscle and white adipose tissue. However, obesity is related with an impaired action of leptin, namely leptin resistance, causing hyperleptinemia and an increase in the energy intake. In this context, the aim of this thesis is to identify phenolic compounds with the capacity to restore the obesogenic-leptin resistance condition caused in peripheral tissues (liver, skeletal muscle and epididymal white adipose tissue) and to increase the leptin transport across the blood-brain barrier. Our results demonstrate the effects of resveratrol and its metabolites acting in the peripheral leptin signalling pathway on reducing body fat accumulation in an obesogenic rat model. Moreover, resveratrol restores the leptin sensitivity in a palmitate-induced model of steatotic human hepatocellular carcinoma cell line by increasing the leptin receptor content. Finally, the capacity of different phenolic compounds to increase the leptin receptor content and to protect against pro-inflammatory cytokine-induced damage in rat brain endothelial cells is described. This research provides novel information that can be useful for the functional food industry identifying bioactive compounds that can be used to potentially treat obesity and its related pathologies.