title: Omega-9 Oleic Acid Induces Fatty Acid Oxidation and Decreases Organ Dysfunction and Mortality in Experimental Sepsis.
abstract: Sepsis is characterized by inflammatory and metabolic alterations, which lead to massive cytokine production, oxidative stress and organ dysfunction. In severe systemic inflammatory response syndrome, plasma non-esterified fatty acids (NEFA) are increased. Several NEFA are deleterious to cells, activate Toll-like receptors and inhibit Na+/K+-ATPase, causing lung injury. A Mediterranean diet rich in olive oil is beneficial. The main component of olive oil is omega-9 oleic acid (OA), a monounsaturated fatty acid (MUFA). We analyzed the effect of OA supplementation on sepsis. OA ameliorated clinical symptoms, increased the survival rate, prevented liver and kidney injury and decreased NEFA plasma levels in mice subjected to cecal ligation and puncture (CLP). OA did not alter food intake and weight gain but diminished reactive oxygen species (ROS) production and NEFA plasma levels. Carnitine palmitoyltransferase IA (CPT1A) mRNA levels were increased, while uncoupling protein 2 (UCP2) liver expression was enhanced in mice treated with OA. OA also inhibited the decrease in 5' AMP-activated protein kinase (AMPK) expression and increased the enzyme expression in the liver of OA-treated mice compared to septic animals. We showed that OA pretreatment decreased NEFA concentration and increased CPT1A and UCP2 and AMPK levels, decreasing ROS production. We suggest that OA has a beneficial role in sepsis by decreasing metabolic dysfunction, supporting the benefits of diets high in monounsaturated fatty acids (MUFA).
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Cassiano Felippe
authors.initials: CF
authors.lastname: Gonçalves-de-Albuquerque
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Isabel Matos
authors.initials: IM
authors.lastname: Medeiros-de-Moraes
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Flora Magno de Jesus
authors.initials: FM
authors.lastname: Oliveira
authors.affiliation: Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, 24020-15 Niterói, RJ, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Burth
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Patrícia Torres
authors.initials: PT
authors.lastname: Bozza
authors.affiliation: Departamento de Medicina Interna, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, 20550-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Mauro Velho
authors.initials: MV
authors.lastname: Castro Faria
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.
authors.forename: Adriana Ribeiro
authors.initials: AR
authors.lastname: Silva
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, 21040-900 Rio de Janeiro, RJ, Brazil.|Universidade Estácio de Sá, Programa de Produtividade Científica, Rio de Janeiro, RJ, Brazil.
authors.forename: Hugo Caire de
authors.initials: HC
authors.lastname: Castro-Faria-Neto
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis; D015996:Survival Rate; D000071246:Uncoupling Protein 2
chemical_list: D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D019301:Oleic Acid; D008315:Malondialdehyde; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases