López-Gómez, CarlosSantiago-Fernández, ConcepciónGarcía-Serrano, SaraGarcía-Escobar, EvaGutiérrez-Repiso, CarolinaRodríguez-Díaz, CristinaHo-Plágaro, AilecMartín-Reyes, FloresGarrido-Sánchez, LourdesValdés, SergioRodríguez-Cañete, AlbertoRodríguez-Pacheco, FranciscaGarcía-Fuentes, Eduardo2022-09-222022-09-222020-08-12López-Gómez C, Santiago-Fernández C, García-Serrano S, García-Escobar E, Gutiérrez-Repiso C, Rodríguez-Díaz C, et al. Oleic Acid Protects Against Insulin Resistance by Regulating the Genes Related to the PI3K Signaling Pathway. J Clin Med. 2020 Aug 12;9(8):2615http://hdl.handle.net/10668/4103The effects of different types of fatty acids on the gene expression of key players in the IRS1/PI3K signaling pathway have been poorly studied. Material and Methods: We analyzed IRS1, p85α, and p110β mRNA expression and the fatty acid composition of phospholipids in visceral adipose tissue from patients with morbid obesity and from non-obese patients. Moreover, we analyzed the expression of those genes in visceral adipocytes incubated with oleic, linoleic, palmitic and dosahexaenoic acids. Results: We found a reduced IRS1 expression in patients with morbid obesity, independent of insulin resistance, and a reduced p110β expression in those with lower insulin resistance. A positive correlation was found between p85α and stearic acid, and between IRS1 and p110β with palmitic and dosahexaenoic acid. In contrast, a negative correlation was found between p85α and oleic acid, and between IRS1 and p110β with linoleic, arachidonic and adrenic acid. Incubation with palmitic acid decreased IRS1 expression. p85α was down-regulated after incubation with oleic and dosahexaenoic acid and up-regulated with palmitic acid. p110β expression was increased and decreased after incubation with oleic and palmitic acid, respectively. The ratio p85α/p110β was decreased by oleic and dosahexaenoic acid and increased by palmitic acid. Conclusions: Our in vitro results suggest a detrimental role of palmitic acid on the expression of gene related to insulin signaling pathway, with oleic acid being the one with the higher and more beneficial effects. DHA had a slight beneficial effect. Fatty acid-induced regulation of genes related to the IRS1/PI3K pathway may be a novel mechanism by which fatty acids regulate insulin sensitivity in visceral adipocytes.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Morbid obesityInsulin resistanceIRS1p85αp110βPalmitic acidOleic acidDocosahexaenoic acidLinoleic acidVisceral adipose tissueObesidad mórbidaResistencia a la insulinaÁcido palmíticoÁcido oléicoÁcidos docosahexaenoicosÁcido linoleicoGrasa intraabdominalAndalucíaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin ResistanceMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Phosphatidylinositol 3-KinasesMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Abdominal Fat::Intra-Abdominal FatMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity::Obesity, MorbidMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::AdipocytesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene ExpressionMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Palmitic AcidsMedical Subject Headings::Chemicals and Drugs::Lipids::PhospholipidsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Stearic AcidsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic AcidsMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, UnsaturatedMedical Subject Headings::Geographical Locations::Geographic Locations::Europe::Spainresearch article32806641open access10.3390/jcm90826152077-0383PMC7463472