Metabolomics strategy to comprehend the interactions between circadian rhythms and flavanol activity on the hepatic metabolism

Identifier:  TDX:3043

Handle: https://hdl.handle.net/20.500.11797/TDX3043

Authors:  Palacios Jordán, Héctor

Abstract:
A grape seed proanthocyanidin extract (GSPE) has been associated with a widely range of beneficial effects for the prevention and treatment of hepatic metabolic disturbances induced by obesity, such as insulin resistance or steatosis. Moreover, GSPE is capable to modulate the clock system in the liver, which is also disrupted in an obesity status, thus suggesting that GSPE can partially regulate lipid and glucose metabolism by modulating the hepatic circadian rhythms. NMR-based metabolomics strategy is an adequate approach to study the interaction between the proanthocyanidin effects and the circadian rhythmicity of the hepatic metabolism. In this regard, this thesis aims to evaluate whether a grape seed proanthocyanidin extract (GSPE) has different effects on the hepatic metabolism depending on the administration time, in a metabolic syndrome situation. The circadian rhythm disruption of the hepatic metabolism, caused by obesity, was studied in both genders in order to elucidate whether this disruption is gender-dependent. Female animals showed to be more resistance and flexible against an obesogenic diet. The chronic administration of GSPE presented different effects in obese male rats depending on its administration time. A large amount of its beneficial effects were found when GSPE was given at the beginning of the light phase. Possible antioxidant effects and an improvement in hepatic insulin sensitivity were only observed in those animals. The results of this thesis elucidate the importance of the administration time of GSPE. Additionally, this thesis shows the better circadian rhythm flexibility of obese female rats.