Resumen de Adipose tissue remodelling by polyphenols in obese rats
The research work of the present thesis is included in the project AGL2013-40707-R “Development of an integrated food to maintain body weight and to prevent the risk of obesity related pathologies” which aims to formulate a MIX, containing several bioactive compounds, useful for the prevention of a set of pathologies that encompass the metabolic syndrome. The final idea is to develop a 2.0 functional food, that will be able to prevent simultaneously all the risk factors associated to a multifactor situation, such as metabolic syndrome (MS). This MIX is based on proanthocyanidins (PAs) complemented with other natural bioactive compounds that are able to improve pathologies associated to obesity and MS. Obesity is already considered the 21st century epidemic and it is socially essential to carry on studies focused on new therapeutic approaches to help counteracting obesity and, with it, the risks to suffer associated complications such as cardiovascular disease and type II diabetes. However, it seems that excess of fat accumulation in obesity is not directly linked with its associated diseases, since some obese individuals are regarded as metabolically healthy. This highlight the importance of the capacity of white adipose tissue (WAT) to expand and then store the energy surplus. Once adipocytes have reached a certain threshold, this storage capacity becomes limited and this is associated with metabolic complications. WAT expansion occurs through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been strongly correlated with obesity-related disorders while hyperplasia has been shown to protect against metabolic disruptions such as insulin resistance and dyslipidaemia. Thus, improving WAT expandability is a good strategy to find new therapies for obesity treatment.
Several polyphenols have been previously described to amend many components of MS and obesity-related disorders even without reducing body weight. Thus, we hypothesised that WAT expandability could be the mechanism through which polyphenols exert their beneficial effects.
This thesis has focused on the evaluation of different polyphenols effectiveness in preventing or counteracting obesity-associated WAT dysfunction associated to obesity through remodelling it. For this, dietary or pharmacological doses of a grape seed proanthocyanidin extract (GSPE), Gallic Acid (GA) or Resveratrol (RSV) were administered orally to rats while rats were made obese by an obesogenic diet or once obesity was noticeable. Histological analysis was performed in subcutaneous and/or visceral WAT fat depots to measure adipocyte area and volume for the further calculation of adipocyte number in fat depots. Moreover, the gene expression of markers of adipogenesis, lipolysis, browning, lipid oxidation and inflammation was analysed in WATs by quantitative RT-PCR. Furthermore, serum metabolites and hormones related to lipid and glucose metabolism were measured by colorimetric and immunometric assays.
Results show that polyphenol with different chemical structures, flavonoids and non-flavonoids, were capable of remodelling adipose tissue in both a preventive and corrective manner in obesity. This remodelling effect was associated to the improvement of lipid and glucose homeostasis. Thus, WAT remodelling could contribute to the beneficial effects of polyphenols in obesity-related diseases and MS.
Although experimental data obtained in rats cannot directly be extrapolated to humans, the results from this thesis suggest that the incorporation of polyphenol-rich foods to the diet or nutraceuticals could be useful for the treatment of metabolic disorders in obesity.
