Álvarez-Amor, LeticiaSierra, Amparo LuqueCárdenas, AntonioLópez-Bermudo, LucíaLópez-Beas, JavierAndújar, EloísaPérez-Alegre, MónicaGallego-Durán, RocíoVarela, Lourdes M.Martin-Montalvo, AlejandroBerná, GenovevaRojas, AnabelRobles-Frías, Mª JoséHmadcha, AbdelkrimRomero-Gómez, ManuelKleemann, RobertMartín, Franz2022-09-062022-09-062021-04-15Álvarez-Amor L, Sierra AL, Cárdenas A, López-Bermudo L, López-Beas J, Andújar E, et al. Extra virgin olive oil improved body weight and insulin sensitivity in high fat diet-induced obese LDLr-/-.Leiden mice without attenuation of steatohepatitis. Sci Rep. 2021 Apr 15;11(1):8250http://hdl.handle.net/10668/4006Dietary fatty acids play a role in the pathogenesis of obesity-associated non-alcoholic fatty liver disease (NAFLD), which is associated with insulin resistance (IR). Fatty acid composition is critical for IR and subsequent NAFLD development. Extra-virgin olive oil (EVOO) is the main source of monounsaturated fatty acids (MUFA) in Mediterranean diets. This study examined whether EVOO-containing high fat diets may prevent diet-induced NAFLD using Ldlr-/-. Leiden mice. In female Ldlr-/-.Leiden mice, the effects of the following high fat diets (HFDs) were examined: a lard-based HFD (HFD-L); an EVOO-based HFD (HFD-EVOO); a phenolic compounds-rich EVOO HFD (HFD-OL). We studied changes in body weight (BW), lipid profile, transaminases, glucose homeostasis, liver pathology and transcriptome. Both EVOO diets reduced body weight (BW) and improved insulin sensitivity. The EVOOs did not improve transaminase values and increased LDL-cholesterol and liver collagen content. EVOOs and HFD-L groups had comparable liver steatosis. The profibrotic effects were substantiated by an up-regulation of gene transcripts related to glutathione metabolism, chemokine signaling and NF-kappa-B activation and down-regulation of genes relevant for fatty acid metabolism. Collectivelly, EVOO intake improved weight gain and insulin sensitivity but not liver inflammation and fibrosis, which was supported by changes in hepatic genes expression.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Extra virgin olive oilInsulin sensitivityBody weightsteatohepatitisLDLDiet, high-fatAceite de olivaResistencia a la insulinaPeso corporalHígado grasoLipoproteínas LDLDieta alta en grasaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body WeightMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-FatMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Diet, MediterraneanMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid MetabolismMedical Subject Headings::Anatomy::Digestive System::LiverMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, KnockoutMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, ObeseMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Lipoprotein::Receptors, LDLMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistanceresearch article33859314open access10.1038/s41598-021-87761-32045-2322PMC8050103