XL Reuniòn Anual de la Sociedad de Biologìa de Cuyo. Mendoza, 6 y 7 de Diciembre de 2022.

FUNES, ABI KARENINA; AVENA, MARÍA VIRGINIA; AGUERO ROCIO; BOARELLI PAOLA VANINA; CONTE, MARÍA INÉS; MONCLUS MARÍA DE LOS ÁNGELES; FORNÉS MIGUEL WALTER; SAEZ LANCELLOTTI TANIA ESTEFANÍA

Congreso; XL Reunion Anual de la Sociedad de Biologia de Cuyo; 2022

Hepatic cholesterol (chol) accumulation induced by lipid overload is a major public health problem worldwide, and natural products suchas Extra Virgin Olive Oil (EVOO) has proven benefits, but the mechanism remains unclear. Sterol regulatory element-binding protein 2(SREBP2) leads intracellular chol metabolism as a transcription factor and is sensitive to dietary fat intake. Our aim was to test the effectsof EVOO addition to high-fat diet (HFD) on the expression of hepatic chol metabolism pathway molecules using rabbits as an experimentalmodel of hypercholesterolemia (HC). New Zealand rabbits were fed a commercial pellet (control), a HFD (14% bovine fat, HC rabbits) orwith a HFD plus EVOO (HFD 7% + EVOO 7%: protected rabbits) up to 12 months. Hepatic chol accumulation was characterized by thespecific marker filipin III. The expression of SREBP2, HMGCR (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) and LDLR (low-density lipoprotein receptor) was studied by western blot and PCR. Our results show that hepatic chol increased in HC rabbits but decreasedin protected animals. SREBP2 mRNA was not modified by HFD although protein expression decreased in the short term, and raised undera long term HFD. When EVOO was added, in both cases the expression increased significantly. HMGCR expression did not varysignificantly with HFD, but increased with the addition of EVOO. LDLR mRNA and protein showed increased with both diets. This resultsindicate that fat intake deregulates SREBP2 expression, leading to lipid accumulation in rabbit hepatocytes. The addition of EVOOprevented fat diet-induced lipid increase despite rising HMGCR and LDLR expression. The former needs further research as it involvesmany post-translational regulators; and the LDLR increase is reasonable as the hepatocyte is the main cell involved in the removal ofplasma cholesterol through LDLR activity. The improvement in hepatic lipid accumulation is probably related to other mechanisms suchas bile production. Finally, all the molecules analyzed here were sensitive to EVOO supplementation, although specific studies are neededto determine the exact mechanism of protection