Polyphenol effects on central leptin sensitivity in obesity

Identificador:  TDX:2647

Handle: https://hdl.handle.net/20.500.11797/TDX2647

Autores:  Ibars Serra, Maria

Resumen:
Obesity is an increasing health problem and a major risk factor for a number of chronic diseases. Up to now, strategies to reduce and prevent obesity were unsuccessful. Therefore, novel approaches to treat obesity need to be developed. In this sense, several animal and human studies demonstrate that polyphenols protect against metabolic disorders including diabetes and cardiovascular disease. Thus, polyphenols emerge as bioactive compounds useful to reduce obesity and its associated metabolic diseases. Energy balance is regulated by leptin in the central nervous system, particularly in the hypothalamus where it activates POMC and inhibits AgRP neurons to produce satiety and promote energy expenditure. However, leptin action appears to be suppressed in obesity which is reflected by increased appetite and reduced energy expenditure. The aim of this thesis was to identify polyphenols that improve leptin sensitivity under obesogenic environments, which could ultimately result in a loss of body weight. We show that a chronic intake of a grape seed proanthocyanidin extract improves leptin signaling by increasing POMC gene expression and reduces food intake without decreasing body weight in obese animals. Furthermore, we investigated other polyphenols that could complement the effects of proanthocyanidins by enhancing body weight loss. Our results show that high doses of resveratrol effectively reduce body weight, fat mass and correct hyperleptinemia in obese animals acting as a leptin sensitizer compound. Additionally, we demonstrate the potential of seasonal fruits rich in polyphenols to modulate hypothalamic leptin signaling and downstream effectors in normal conditions and during obesity. Finally, the role of a novel target to modulate AgRP neurons activity is explained. The outcome of this research provides insights into the design of functional foods that combine bioactive compounds which could potentially be used as anti-obesity therapy.