Intervention Of Leucine And Complex Protein Peptide On Energy Metabolism Disorder In Animals Induced By High Fat Diet

ObjectiveOverweight and obesity are independent risk factors for chronic non-communicable diseases,including type 2 diabetes,non-alcoholic fatty liver(NAFLD),cardiovascular disease and so on.In recent years,the incidence of overweight and obesity has been increasing,which has become a major public health problem in China.Thus,it is of great practical significance to explore the new intervention measures for energy metabolism disorders of human being,especially based on dietary components.Studies proved that leucine is closely related to energy metabolism,but the evidences is inconsistent.In this study,leucine supplementation on the adipose tissue and energy metabolism of the mice fed with either chow diet or high fat diet were observed.Subsequently,the leucine-rich protein peptide was prepared and its beneficial effects on glucose and lipid metabolism of obese rats induced by high fat diet were investigated.MethodsMale C57BL/6J mice were fed with either chow diet or high fat diet,half of mice in each diet group were received 1.5%leucine via drinking water last for 24 weeks.The body weight,blood glucose and lipids of mice treated with or without leucine were analyzed,as well as the hepatic fat accumulation detected by oil red O staining.Oxymas/CLAMS Columbus instrument was employed to monitor and record the animal energy metabolism under different treatments.Western blot was used to detect the expression of fatty acid synthase(FAS)and fatty acid binding protein(FABP4),the activation of adenosine-activated protein kinase(AMPK)by phosphorylation,the expression of SIRT1,and the activity of branched-chain αketo dehydrogenase E1α(BCKDE1A)in mouse liver.Diet-induced obesity rat model was used.SD male rats were fed with high fat diet,then the rats were given feed adding different proportion leucine-rich protein peptide last for 30 days.The changes of the body weight,body fat mass and hepatic lipids of obese rats were observed.The glucose tolerance test(GTT)and insulin tolerance test(ITT)were used to evaluate the glucose tolerance and insulin sensitivity,oil red O staining employed to reveal the hepatic fat of the obese rats treated with or without the leucine-rich protein peptide.The phosphorylation activation of hormone-sensitive lipase(HSL),expression of triglyceride lipase(ATGL),mitochondrial oxidative phosphorylation(OXPHOS)complex and uncoupling protein 1(UCP1)in adipose tissue were also analyzed by Western blot in rats.ResultsThe body weight of mice fed with high fat diet increased significantly.The leucine supplementation significantly reduced the weight gain,the levels of blood glucose and lipids,and the hepatic lipids of animals fed with high fat diet to a certain extent.Co-treatment high fat diet with leucine significantly increased the O2 consumption,CO2 production and heat expenditure,and decreased the respiration exchange rate(RER)of high fat fed animals,indicated the enhancement of the energy metabolism.Leucine treatment significantly downregulated the expression of FAS and FABP4,enhanced the phosphorylation activation of AMPK,increased the expression of SIRT1 and PGC-1α of hepatic tissues of obese mice,and markedly reversed the phosphorylation of BCKDE1A in liver induced by high fat diet.Diet-induced obese rats were fed with leucine-rich complex protein peptide for 30 days,the body weight,white adipose tissue and hepatic lipid of obese rats induced by high fat diet was significantly reduced under treatment with leucine-rich protein peptide,with dosedependent manner.The blood glucose and blood lipids of rats decreased significantly,but glucose tolerance and insulin sensitivity kept unchanged.In addition,p-HSL level and ATGL expression were increased in white adipose tissue and brown adipose tissue,and mitochondrial OXPHOS and UCP1 expression were also significantly up-regulated in brown adipose tissue.Conclusions1.Long-term leucine supplementation of mice could promote the energy expenditure,effectively reduce weight gain,attenuate the fat accumulation,and decrease the levels of blood glucose and lipids of mice fed with high fat diet,which might be related to the activation of liver AMPK-SIRT1 pathway that further to prompt the mitochondrial genesis,decrease the fatty acid synthesis,as well as enhance the hepatic leucine catabolism.2.Leucine-rich protein peptide could reduce the body weight and white adipose tissue,attenuate the hepatic fat accumulation,and decrease plasma lipid in obesity rats induced by high fat diet,which might be attributed to the increase of lipolysis and thermogenesis.That were supported by the increase of HSL phosphorylated activation and the expression of ATGL of white and brown adipose tissue,as well as the increase of expression of mitochondrial oxidative phosphorylation complex and UCP1 in brown adipose tissue from obese rats administered with leucine-rich protein peptide.