Hipertrigliceridèmia en un model dietètic d’esteatosi hepàtica en rata : modulació per pemafibrat

Treball Final de Grau de Bioquímica. Facultat de Biologia. Universitat de Barcelona, Curs: 2022-2023, Tutora: Dra. Marta Alegret ; V Premi Clara Campoamor al millor Treball Final de Grau amb perspectiva de gènere de la Universitat de Barcelona, curs 2021-2022. Accèssit. Branca de Ciències Experimentals ; [eng] Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by the accumulation of triglycerides, forming lipid droplets in hepatocytes, in the absence of excessive alcohol consumption. It is the most common liver disease worldwide and affects 25% of the population, primarily developing in patients with other metabolic disorders such as obesity, diabetes, or high cholesterol. There is evidence suggesting that NAFLD can be prevented and treated with physical activity and dietary changes, but currently there is no approved pharmacological treatment for NAFLD. For this reason, a dietary model of fatty liver was developed in female rats to investigate an effective pharmacological therapy for treating early stages of the disease. To study the effect of pemafibrate, three groups of female Sprague Dawley rats with different experimental conditions were used: a standard diet (CT), a high-fat diet supplemented with 10% w/v fructose in drinking water (HFD-HFr), and a HFD-HFr diet with pemafibrate (Pema). Despite the PPAR-α agonist effect of pemafibrate, an increase in blood triglyceride levels contrary to what the literature suggested was observed. To determine the cause of this hypertriglyceridemia, we explored pathways related to lipoprotein synthesis and export, as well as to blood triglyceride catabolism. Western blot, RT-qPCR, and ELISA techniques were used to analyse the levels of the proteins PNPLA3, UCP1, and ANGPTL3, as well as the expression of genes encoding MTTP and LPL. The results revealed that the export of VLDL was not significantly affected by the presence of the drug, but the significant increase in the levels of ANGPTL3, which inhibits lipoprotein lipase, suggests a decrease in the ...