Study On The Mechanism Of Pomegranate Punicalagin Regulating Fat Metabolism And Obesity Resistance Based On AMPK Pathway

Objective: To study punicalagin’s impact on controlling fat metabolism,obesity resistance,and its molecular mechanism is the goal.Method: The C57BL/6J mice were split into the normal group and the model group at random.For 12 weeks,the model group consumed a high-fat diet whereas the regular group consumed a traditional diet.The mice were once again randomly assigned to the model group,the Orlistat group,the punicalagin low dosage group,the punicalagin medium dose group,and the punicalagin high dose group after 12 weeks.For eight weeks,each medication group received varied concentrations of pomegranate and the positive control drugs Orlistat by gavage,along with filtered water for the normal group and model group.Every week,changes in mouse weight and food consumption were noted,and Lee’s index was tracked.After 8 weeks,the trends in organ coefficients and fat coefficients were examined,the four blood lipid indexes,the liver function,the serum glucose were found,the pathological state of the liver and adipose tissue cells was seen by HE staining,and fasting blood sugar,random blood sugar,glucose tolerance,and insulin sensitivity were found.In the liver and adipose tissue,RT-q PCR was used to measure the m RNA expression levels of genes linked to fat metabolism and the AMPK signal pathway,and Western blotting was used to measure the expression levels of proteins associated to the AMPK signal pathway.Results: The body weight,the Lee’s index,the aliphatic index,the serum TC,TG and LDL-C contents were significantly higher in the model group than the normal group(P<0.05),while HDL-C contents were significantly lower than those in the normal group(P<0.01),the hepatic function index appeared abnormal(P<0.01),a large number of fat vacuoles appeared in liver and adipose tissue,and fat deposition was increased,fasting blood glucose and random blood glucose were increased(P<0.01),glucose tolerance and insulin sensitivity were abnormal(P<0.01).The m RNA content expression of PPARγ,C/EBPα and ACC were significantly increased in liver and adipose tissue(P<0.05,P<0.01),and the m RNA expressions of AMPK and CPT1α were significantly decreased(P<0.05,P<0.01);ACC protein expression was significantly increased in liver and adipose tissue(P<0.01),and p-AMPK and CPT1 A protein expressions were significantly decreased(P<0.05,P<0.01).After treatment with different concentrations of drugs,the above indexes of obese mice were significantly reversed,the body mass caused by high fat diet was decreased slowly and significantly(P<0.05);The intake of punicalagin intervention group were also decreased significantly(P<0.05,P<0.01);The Lee’s index of punicalagin intervention group and orlistat group were decreased significantly(P<0.01);The fat coefficient of the punicalagin intervention group and the orlistat group were decreased significantly(P<0.05,P<0.01);The content of TG in serum of obese mice was significantly decreased in different doses of punicalagin(P<0.05,P<0.01);The content of serum TC in obese mice was significantly decreased in each dose group of punicalagin(P<0.05,P<0.01);For HDL-C,punicalagin glycoside in all dose groups were increased significantly(P<0.01);For LDL-C,punicalagin intervention group was significantly decreased(P<0.05,P<0.01);The liver function indexes of the punicalagin intervention group and the orlistat group tended to be normal(P<0.01);Compared with the model group,the hepatocytes in the high-dose group of punicalagin glycoside and orlistat group were arranged orderly,with clear structure and significantly reduced lipid vacuolation rate;After high dose of punicalagin and orlistat,the adipose tissue of mice showed uniform distribution,its particle size was smaller than that of model group,and the volume of individual cells was smaller;For the fasting blood glucose and random blood glucose,the fasting blood glucose level of the punicalagin intervention group and the orlistat group were significantly lower than that of the model group(P<0.01),and the glucose tolerance and insulin sensitivity also tended to be normal(P<0.01);The m RNA expression of PPARγ,C/EBPα and ACC in liver and adipose tissues were significantly decreased(P<0.01)and the m RNA expression of AMPK and CPT-1α were increased to varying degrees in each of the punicalagin intervention groups(P<0.05,P<0.01);the protein expression of p-AMPK and CPT1 A in liver and adipose tissues were significantly increased(P<0.01)and the expression of ACC was significantly decreased in each of the punicalagin intervention groups(P<0.01).Conclusion: Punicalagin,a refined pomegranate skin product,may effectively restrict the food intake in obese mice and control aberrant blood lipid,fat,and blood glucose metabolism associated with obesity.Punicalagin regulates changes in fat metabolism by modulating the expression of genes and proteins linked to the production and breakdown of hepatic adipose tissue.Punicalagin may down-regulate lipid synthesis and up-regulate lipid decomposition through activating AMPK pathway.The activation of the AMPK signal pathway in the liver and adipose tissue may be connected to its method of controlling lipid metabolism.