Ana Magdalena Velázquez, Spain
University of Barcelona Pharmacology, Toxicology and Therapeutic ChemistryPresenter of 1 Presentation
Effects of bempedoic acid on diet-induced hepatic steatosis in female rats
Abstract
Background and Aims
Bempedoic acid (BemA), an ATP-citrate lyase (ACLY) inhibitor, reduces cholesterol and fatty acid synthesis. We explored BemA effects in the early stage of non-alcoholic fatty liver disease in a diet-induced rat model of hepatic steatosis.
Methods
Eight-week-old female Sprague-Dawley rats were randomly distributed into 3 groups (n=8): control (CT; standard rodent chow), fructose plus high fat diet (FHFD; high fat diet and 10% w/v fructose in drinking water), and FHFD plus BemA at 30 mg/Kg/day (BemA). All rats were fed the diets for three months, and BemA group was treated orally with BemA for the last month. Biochemical and zoometric parameters were determined. Beta-oxidation activity and gene/protein expression were determined in hepatic tissue.
Results
FHFD rats consumed almost twice more calories than controls, but their body weight at the end of treatment was not increased. Significant hepatic triglyceride accumulation and hypertriglyceridemia were observed in FHFD rats. Treatment with BemA reduced hepatic triglyceride accumulation and increased liver weight in comparison to FHFD. Histological images showed an increase of hepatocyte size in Bem A group in comparison to the other groups. Beta-oxidation activity was reduced in FHFD group, and treatment with BemA not only blunted this effect, but also caused a significant increase of this enzyme activity in relation to FHFD. Accordingly, BemA markedly induced the hepatic gene expression of acyl-CoA oxidase (ACO), without changes in carnitine palmitoyl transferase 1 (CPT1).
Conclusions
BemA may induce hepatic peroxisomal proliferation and reduce hepatic steatosis at least in part through increased fatty acid catabolism.