ABSTRACT
Aim To explore the effeet of riboflavin on the establishment of pressure overload-induced heart failure model in mice by thoracic aortie constrietion (TAC ) and its preventive mechanism.Methods Eight-week-old SPF C57BL/6J mice were seleeted and divided into four groups; Sham group.Sham + ribofla¬vin group, TAC group and TAC + riboflavin group.A mouse heart failure model was constructed in the TAC group.The miee in the TAC + riboflavin group were given riboflavin by gavage one week before and eight weeks after the operation.The cardiac ultrasound inde¬xes, the changes of cardiac morphology and mitochon¬drial function indexes, the expression of apoptosis pro¬teins, ATP content, SCAD mRNA and protein expres¬sion, enzyme activity and flavin adenine dinucleotide (FAD) content in myocardial tissues were detected.Hie free fatty acid content in serum and myocardial tis¬sues were also detected.Results Compared with the sham group, the cardiac function indexes of the mice in the TAC group decreased, anrl typical heart failure occurred.Moreover, the expression of SCAD, enzyme activity, ATP and FAD content in the myocardium sig-nificantly decreased, and the free fatty acid content in myocardium and serum significantly increased.Com¬pared with the TAC group, after riboflavin treatment, the cardiac function of mice in TAC + Riboflavin group was significantly improved.In addition, ATP content, SCAD expression, enzyme activity and FAD content in myocardium all significantly increased, and free fatty acid content in myocardium and serum markedly de¬creased.Conclusions Riboflavin may improve myo-cardial energy metabolism by increasing FAD content and activating SCAD, thereby inhibiting pressure over¬load-induced heart failure in mice.
ABSTRACT
Aim To investigate the effects of overexpression of short-chain acyl-CoA dehydrogenase (SCAD) recombinant adenovirus on heart failure following myocardial infarction in rats, and to explore the relationship between SCAD and heart failure. Methods The rat model of heart failure following myocardial infarction was established by ligation of left anterior descending coronary artery (LAD). The SCAD recombinant adenovirus was injected into the apical wall. The experimental groups were divided into 6 groups; Sham + NS group, LAD + NS group, Sham + Ad-GFP group, Sham + Ad-SCAD group, LAD + Ad-GFP group and LAD + Ad-SCAD group. Systolic blood pressure (SBP) of tail artery was measured after surgery and the cardiac morphological changes were detected. The changes of SCAD mRNA expression, protein expression, enzyme activity, ATP content and free fatty acid content were examined. Results Compared with sham group, LAD + NS group showed heart failure significantly. Compared with LAD + NS group, SBP from LAD + Ad-SCAD group increased obviously after surgery, collagen deposition was apparently reduced and myocardial fibrosis was markedly improved. Compared with Sham + NS group, the SCAD mRNA, protein expression, enzyme activity and ATP content in LAD + NS group obviously decreased, and the contents of free fatty acids markedly increased. Compared with LAD + NS group, the above indicators of LAD + Ad-SCAD group were evidently reversed after treated with SCAD recombinant adenovirus. Conclusion Overexpression of SCAD recombinant adenovirus in heart can significantly improve heart failure caused by LAD.
ABSTRACT
()of recessive hereditary diseases caused by the dysfunction of enzymes required for fatty acids to enter mitochondria or fatty acid beta-oxidation,including carnitine transport disorders and fatty acid beta-oxidation disorders. Clinical symptoms are non-specific,involving multiple organs,such as liver,myocardium,skeletal muscle,brain and kidney. Most FAOD patients diagnosed by newborn screening have no clinical symptoms or mild symptoms through early intervention management,but they are prone to acute onset or even sudden death under stress conditions such as hunger and exercise. Long-term follow-up and management can effectively reduce the mortality and morbidity rate of FAOD.
ABSTRACT
Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.
Subject(s)
Humans , Acetyl Coenzyme A/metabolism , Fatty Acids/metabolism , Fatty Liver/metabolism , Lipogenesis , Mitochondria/metabolism , Triglycerides/metabolismABSTRACT
Inborn errors of fatty acid mitochondrial oxidation (FAOD) have drawn considerable attention in recent years because of rapid pace of discovery of new defects and an ever-increasing spectrum of clinical phenotypes. This review describes a clinical and biochemical phenotypes, diagnosis and treatment of FAOD. Some of FAOD can not be detected by conventional biochemical investigations, even when a patient is symptomatic with fasting intolerance or functional failure of fatty acid dependent tissue (s). Diagnosis must ultimately be based on direct assay of the involved enzyme, however, preliminary indicators may come from determination of carnitine and intermediate metabolites in plasma, profiling of urine organic acid, and radioisotopic screening assays with lymphocytes or cultured fibroblasts. We are faced with the following major challenges: whether to include FAOD in newborn screening programs, the investigation of the rules played by individual disorders in maternal complication during pregnancy, sudden and unexpected death in early life, and pediatric acute/fulminant liver failure.