The influence of biological rhythms on the beneficial effects of grape seed proanthocyanidin extract (GSPE) on liver metabolism in health and disease

Identificador:  TDX:4103

Handle: https://hdl.handle.net/20.500.11797/TDX4103

Autores:  Rodriguez, Romina Mariel

Resumen:
Biological rhythms are internal timing mechanisms that allow organisms to adapt and anticipate cyclical changes in the environment caused by the rotation of the earth around its axis (circadian rhythms) and around the sun (circannual rhythms). Disruption of these mechanisms have been associated with impairment of metabolic homeostasis. Nowadays, excessive consumption of high-calorie foods has not only been shown to promote metabolic dysfunction, but also to cause circadian disturbances leading to Metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD). Proanthocyanidins, including grape seed proanthocyanidin extract (GSPE), are secondary plant metabolites that are considered beneficial in treating metabolic diseases. It has been reported that GSPE is able to modulate the circadian clock machinery, thus influencing the internal rhythmicity of metabolic processes. Therefore, the main aim of the present thesis was to evaluate if diurnal rhythms (day/night) and seasonal rhythms (photoperiods) can influence the beneficial effects of GSPE consumption on liver metabolism. To fulfill this objective, we carried out animal experiments and analyzed lipid and glucose-related parameters in blood and liver in relationship with the liver clock function. Firstly, we assessed the alteration of the hepatic metabolic rhythms caused by an obesogenic diet intake and demonstrated that the restorative effect of GSPE depends on the timing of administration. Most of its beneficial effects were found when GSPE was administered at the onset of the dark phase, the beginning of the active phase in rats. Secondly, we determined the photoperiod-dependent response of GSPE effects over serum hormones and liver metabolism under physiological conditions. Finally, we evidenced the strong influence of day length on the beneficial effects of GSPE consumption to treat MS and NAFLD. These findings highlight the importance of considering biological rhythms when studying the therapeutic actions of proanthocyanidins in MS-associated diseases in order to maximize their benefits.