RESUMEN
Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, has previously been shown to ameliorate obesity-associated metabolic syndrome. To decipher the mechanism responsible for the beneficial effects of DHA on energy/glucose homeostasis and the metabolic syndrome, 30 weaned cross-bred pigs were randomly assigned to three groups and fed ad libitum with a standard diet supplemented with 2% of beef tallow, soybean oil or DHA oil for 30 days, and the gene expression profile of various tissues was evaluated by quantitative real-time polymerase chain reaction. The DHA-supplemented diets reduced the expression of forkhead box O transcription factor (FoxO) 1 and FoxO3 in the liver and adipose tissue. DHA treatments also decreased the expression of FoxO1 and FoxO3 in human hepatoma cells, SK-HEP-1 and human and porcine primary adipocytes. In addition, DHA also down-regulated FoxO target genes, such as microsomal triacylglycerol transfer protein (MTP), glucose-6-phosphatase, apolipoprotein C-III (apoC-III) and insulin-like growth factor binding-protein 1 in the liver, as well as reduced total plasma levels of cholesterol and triacylglycerol in the pig. Transcriptional suppression of FoxO1, FoxO3, apoC-III and MTP by DHA was further confirmed by reporter assays with each promoter construct. Taken together, our study indicates that DHA modulates lipid and glucose homeostasis in part by down-regulating FoxO function. The down-regulation of genes associated with triacylglycerol metabolism and very low density lipoprotein assembly is likely to contribute to the beneficial effects of DHA on the metabolic syndrome.
Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Factores de Transcripción Forkhead/genética , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/genética , Adipocitos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Colesterol/sangre , Suplementos Dietéticos , Femenino , Proteína Forkhead Box O1 , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/metabolismo , Glucosa/metabolismo , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Porcinos/genética , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
Ruthenium complexes with similar octahedral structures but different intrinsic inductive properties significantly influence the total cellular protein distributions, which may affect different metabolic pathways. A systematic study of the relationship between ruthenium complexes and Escherichia coli was undertaken, using two-dimensional gel electrophoresis analysis and the identification of various proteins by mass data mining. Based on the low similarities (<40%) between the total protein distributions, the inductive properties of the ruthenium complexes are relevant to the formation of the protein-Ru interaction in addition to the Ru-DNA interaction. Two major protein functions in E. coli BL21 that were reduced by compound 1 were oxidoreductases and transporters, corresponding to 29% and 25% of the 24 down-regulated proteins. The main biological processes of the proteins down-regulated by compound 1 were related to carbohydrate reactions, including in transport, tricarboxylic acid (TCA) cycle, glycolysis, and gluconeogenesis. All four ruthenium complexes shared similar up-regulated proteins, including clpB and kpyk1, and down-regulated similar proteins, including ompA and ybbN. This result supports that the presence of Ru-protein interactions is a major factor affecting bacteria growth, and particularly transport and carbohydrate-related reactions.
