The Mechanism And Effect Of Leptin Receptor Deficiency On Liver And Kidney Function In Mice

BackgroundDiabetes is a metabolic disorder caused by a variety of factors such as heredity,environment and autoimmune.Persistent hyperglycemia leads to the development of chronic diseases.The threat of diabetes to human health is becoming more and more serious.The incidence rate is increasing worldwide.Lipoic acid（LA）is a powerful antioxidant.Many researches have been done about the biological functions of lipoic acid,but lipoic acid is relatively rare in mammalian metabolism.Lipoic acid is synthesized in mitochondria by lipoic acid synthetase（LIAS）,and its role is closely related to the expression of lipoic acid synthetase.Leptin receptor deficient Lepr^db/db mice block the leptin signaling pathway,increase food intake and decrease heat production,resulting in obesity in mice,which is similar to the occurrence process of type 2 diabetes in humans.At present,the relationship between the action of leptin and lipoic acid synthetase is not clear,and the study of the expression of LIAS protein in Lepr^db/db mice has not yet been reported.ObjectiveTo investigate whether the metabolic disorder of glucose and lipid metabolism in mice caused by the blocking of leptin signaling pathway is related to the expression of LIAS protein,and to test expression of LIAS in liver and kidney of Lepr^db/db mice whose leptin receptor is deficient.provides a new stategy for the prevention and treatment of obesity and diabetes.MethodsRespectively 16 male Lepr^db/+mice and Lepr^db/db mice（n=8,for each group）were included this study which were 10 weeks old.The weight of two groups of mice was measured.Fasting blood glucose（FPG）was measured with blood glucose test strips for all mice after fasting 8h.Blood samples were obtained were from abdominal aorta and the animals were sacrificed.The livers and kidneys were weighed.The right lobe of liver and the left kidney were fixed with 4%paraformaldehyde for pathological examination.Serum samples were separated and the contents of total cholesterol（T-CHO）,triglyceride（TG）,high-density lipoprotein（HDL）,low density lipoprotein（LDL）,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,serum creatinine（SCr）,blood urea nitrogen（BUN）and C reactive protein（CRP）in serum were detected by kit.The mitochondria of liver and kidney were extracted by mitochondrial Isolation kit,and the protein was extracted.The expression of LIAS protein was detected by Western blot method.Results1.Including mesangial cells and mesangial matrix increased such as pathological changes.The FPG,T-CHO,TG,LDL,AST,and CRP of Lepr^db/db mice were increased compared with those of Lepr^db/+mice,the difference was statistically significant（P<0.05）.2.Histopathology observation showed that liver and kidney of Lepr^db/+mice have intact and clear structure.But liver cells of Lepr^db/db mice showed fatty degeneration,glomerular hypertrophy,basement membrane thickening,mesangial area widened.3.Compared with Lepr^db/+mice,LIAS protein expression was increased in liver and kidney mitochondria of Lepr^db/db,the difference was statistically significant（P<0.05）.ConclusionsThere is disorder of glucose and lipid metabolism in the Lepr^db/db mice whose leptin receptor is deficient,and the expression of LIAS protein in liver and kidney of the Lepr^db/dbb/db mice is higher than that of Lepr^db/+mice.The increased expression of LIAS protein may be related to the increased oxidative stress in Lepr^db/db mice than in Lepr^db/+mice.This will provide new ideas for the anti-oxidation treatment of diabetes.