Mechanism Of Dicarboxylic Acid Promoting Cholesterol Synthesis By Activating Hepatic Peroxisomal β-Oxidation

In this study,we investigated the effect of dicarboxylic acid on cholesterol synthesis in rats by peroxisomeβ-oxidation,and preliminarily explored the mechanism of dicarboxylic acid metabolism on cholesterol synthesis.The experimental group（group D）used healthy male SD rats,fed with dodecanediic acid(DC₁₂)diet for 3 weeks,and decanoic acid(C₁₀)diet as control group（group M）.After the experiment,the plasma and liver of the rats were dissected for analysis.Results show that compared with the control group,DC₁₂ feed of the experimental group significantly increased the weight of the rat,rat liver hypertrophy,making slice observation of liver have a large number of micro bubble drops of fat,plasma glucose and insulin were significantly reduced,plasma and liver triglyceride（TG）were significantly increased,a significant rise in the liver total cholesterol（TC）,Plasma TC and low density lipoprotein（LDL-C）were significantly increased,while high density lipoprotein（HDL-C）was not significantly different between the two groups,indicating that DC₁₂ resulted in increased cholesterol synthesis and fat accumulation in the liver of rats.Further analysis showed that the activity of peroxisome lipoyl-coa oxidase（ACOX1）was significantly increased,and A large amount of peroxisomeβ-oxidation products such as H₂O₂ and ROS were accumulated in liver,indicating that DC₁₂ was mainly metabolized in peroxisome.Compared with control group,the fed DC₁₂made a marked increase in the mitochondrial NADH/NAD⁺,ketone body production decline,explain DC₁₂ beta oxidation in peroxidase,metabolic product of accumulation,the activation of the peroxidase beta oxidation negative regulation of mitochondrial beta oxidation,lipid accumulation and further to cause ascension peroxidase body fatty acid oxidation.Compared with decanoic acid feeding group,peroxidase DC₁₂ feeding group rats body of acetyl-coa hydrolase（ACOT12）activity significantly enhanced,and no significant change in the cytoplasm hydrolase,acetic acid content increased significantly,showed that DC₁₂peroxidase body acetyl-coa beta oxidation products by acetyl coa hydrolysis enzyme hydrolysis,generate acetic acid released into the cytoplasm,The content of acetyl-Co A increased significantly.Western blot results showed that DC₁₂metabolism caused A decrease in AMPK phosphorylation level,leading to A significant increase in the activity of hydroxymethylglutarate Co A reductase（HMGCR）,one of its downstream target proteins,which is A key enzyme for cholesterol synthesis,thus promoting the accumulation of acetyl Co A in the cytoplasm to be transformed into cholesterol.In conclusion,exogenous peroxisomeβ-oxidation inhibits mitochondrial fatty acidβ-oxidation,resulting in lipid accumulation.On the other hand,it promoted the formation and release of peroxisomeβ-oxidation product acetic acid into the cytoplasm,and increased the content of acetyl Co A,the precursor of cholesterol biosynthesis,resulting in increased cholesterol synthesis.