RESUMO
Metabolic profiling studies have highlighted increases in the plasma free fatty acid (FFA) and branched-chain amino acid (BCAA) concentrations, which are hallmarks of the obese and insulin-resistant phenotype. However, little is known about how the increase of the BCAA concentration modifies the metabolic fate of FFA, and vice versa, in adipocytes. Therefore, we incubated differentiated 3T3-L1 adipocytes or primary adipocytes from rats fed a control or a high-fat diet with: (1) 0, 250, 500 and 1000 µM of leucine and determined the oxidation and incorporation of [1-14C]-palmitate into lipids or proteins or (2) 0, 250, 500 or 1000 µM of palmitate and evaluated the oxidation and incorporation of [U-14C]-leucine into lipids or proteins. Leucine decreased palmitate oxidation and increased its incorporation into the lipid fraction in adipocytes; the latter was reduced in adipocytes from obese rats. However, palmitate increased leucine oxidation in adipocytes as well as reduced leucine incorporation into the protein and lipid fractions in adipocytes from obese rats. These results demonstrate that leucine modifies the metabolic fate of palmitate, and vice versa, in adipocytes and that the metabolic interaction between leucine and palmitate catabolism is altered in adipocytes from obese rats.
Assuntos
Adipócitos/metabolismo , Leucina/metabolismo , Obesidade/metabolismo , Palmitatos/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Carnitina O-Palmitoiltransferase/genética , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Leucina/administração & dosagem , Leucina/farmacocinética , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Proteínas de Membrana Transportadoras/genética , Camundongos , Transportadores de Ácidos Monocarboxílicos , Obesidade/patologia , Palmitatos/administração & dosagem , Palmitatos/farmacocinética , Enzima Bifuncional do Peroxissomo/genética , Ratos Endogâmicos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The fatty acid profile is associated with the risk and progression of several diseases, probably via mechanisms including its influence on gene expression. We previously reported a correlation between ECHDC3 upregulation and the severity of acute coronary syndrome. Here, we assessed the relationship of serum fatty acid profile and ECHDC3 expression with the extent of coronary lesion. METHODS: Fifty-nine individuals aged 30 to 74 years and undergoing elective cinecoronariography for the first time were enrolled in the present study. The extent of coronary lesion was assessed by the Friesinger index and patients were classified as without lesion (n = 18), low lesion (n = 17), intermediate lesion (n = 17) and major lesion (n = 7). Serum biochemistry, fatty acid concentration, and ECHDC3 mRNA expression in blood were evaluated. RESULTS: Elevated serum levels of oleic acid and total monounsaturated fatty acids were observed in patients with low and intermediate lesion, when compared to patients without lesion (p < 0.05). ECHDC3 mRNA expression was 1.2 fold higher in patients with low lesion than in patients without lesion (p = 0.020), and 1.8 fold lower in patients with major lesion patients than in patients with low lesion (p = 0.023). CONCLUSION: Increased levels of monounsaturated fatty acids, especially oleic acid, and ECHDC3 upregulation in patients with coronary artery lesion suggests that these are independent factors associated with the initial progression of cardiovascular disease.
Assuntos
Doenças Cardiovasculares/genética , Ácidos Graxos Monoinsaturados/metabolismo , Ácido Oleico/metabolismo , Enzima Bifuncional do Peroxissomo/biossíntese , Adulto , Idoso , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Ácido Oleico/genética , Enzima Bifuncional do Peroxissomo/genética , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: The effects of different amounts of omega 3-polyunsaturated fatty acids in diets with normal or high content of fat on lipid and carbohydrate metabolism were investigated. DESIGN AND METHODS: Mice were fed for 8 weeks on diets enriched with fish oil or lard at 10% or 60% of energy. Energy balance and energy expenditure were analyzed. Fatty acid (FA) oxidative capacity of the liver and the activity of enzymes involved in this pathway were assessed. RESULTS: Fish oil-fed mice had lower body weight and adiposity compared with lard-fed animals, despite having lower rates of oxygen consumption. Mice fed diets containing fish oil also displayed lower glycemia, reduced fat content in the liver, and improved glucose tolerance compared with lard-fed animals. The fish oil-containing diets increased markers of hepatic peroxisomal content and increased the generation of metabolites derived from FA ß-oxidation in liver homogenates. In contrast, no changes were observed in the content of mitochondrial electron transport chain proteins or carnitine palmitoyl transferase-1 in the liver, indicating little direct effect of fish oil on mitochondrial metabolism. CONCLUSION: Collectively, our findings suggest that the energy inefficient oxidation of FAs in peroxisomes may be an important mechanism underlying the protection against obesity and glucose intolerance of fish oil administration.
Assuntos
Dieta , Óleos de Peixe/administração & dosagem , Intolerância à Glucose/prevenção & controle , Obesidade/prevenção & controle , Enzima Bifuncional do Peroxissomo/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/metabolismo , Gorduras na Dieta/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos Ômega-3/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , OxirreduçãoRESUMO
Newborn was referred with diagnosis of neonatal epilepsy. Medical team could suspect and confirm D-bifunctional peroxisomal enzymatic deficiency diagnosis. It was made by family antecedents, severe neonatal hypotonia, uncontrolled neonatal seizures, craniofacial dysmorphic features, psychomotor retardation, neuronal migration defect and a positive peroxisomal panel. The full study in skin fibroblasts involved enzyme analysis, complementation studies and DNA analysis. The accumulation of very long chain fatty acids, partial deficiency in phytanic acid oxidation, and abnormal morphology of peroxisomes was consistent with a defect in peroxisomal fatty acid oxidation, involving D-bifunctional protein. It is very important to make a diagnosis of this innate error of metabolism in order to give preconceptional genetic counseling, to identify recurrence risk and to perform mutation analysis for the D-bifunctional protein gene, and to offer the prenatal diagnosis.