| ObjectiveTo understand of the important role of the physiological characteristics of gallbladder and bile acids in regulating the body’s nutrient metabolism and maintaining the balance of physical and functional activities of the human body.The present study aimed to investigate the mechanism of the role of gallbladder in the formation of obesity.In traditional It was proposed for the first time that the gallbladder and choledochal function disorder(unfavorable bile duct,bile disorder)is the core of obesity.The treatment was through regulating gallbladder functions according to the theory of gallbladder in traditional Chinese medicine.Meanwhile the obesity is classified into a special type of accumulation category.Therefore,the theory of "treating obesity from gall" is put forward,and the prescription of Li-dan-ruan-jian formula is made up of this theory.In this study,a theoretical discussion and experimental study on the treatment of obesity from gall theory was carried out to verify the correlation between bile acids profiles change and the occurrence of obesity.And then investigate the effect of Li-dan-ruan-jian formula in DIO rats and the metabolic mechanism of action.MethodsMale SD rats were fed with high fat diet to induce obesity-prone(OP)and obesity resistance(OR)models.The differences of intake and excretion of food and lipid metabolism were evaluated.The bile acid metabolism profile in bile,serum and feces was determined by Ultraperformance liquid chromatography coupled with quadrupole mass spectrometry(UPLC-MS).Diet induced obesity rats(DIO),were induced by high fat diet.Lipid metabolism analysis,liver pathological section analysis and UPLC-MS technique were used to detect bile and serum in rats.The content of total bile acid in feces and the proportion of bile acid components in feces were evaluated to evaluate the effect of Li-dan-ruan-jian formula(LD)on reducing fat accumulation and regulating the profile of bile acid metabolism in DIO rats.Gene expression analysis was used to study the molecular mechanism of Li-dan-ruan-jian formula in reducing lipid and body weightResults1.The model of high-fat diet-induced obesity(OP)and obesity-resistant(OR)rats were found that in the case of the same intake,the OP rats showed white fat and liver lipid accumulation in the abdomen,the blood lipid and the liver fat were significantly higher than that of the chow group,and the excretion of urine and feces was significantly reduced.The amount of TG in the obese rats was significantly increased and the level of blood lipids was maintained at the normal level.2.In the aspect of total bile acid content,the bile acid synthesis in the obese rats is obviously insufficient,and the loss of bile acid in the feces is increased,and the in-vivo bile acid pool is reduced;the obesity-resistant rat has the remarkable increase of bile acid synthesis,the excretion of the bile acid feces is obviously reduced,and the open source throttling increases the bile acid pool.In that proportion of bile acid,the proportion of bile acid in the bile of the OR rat was changed to the main,and the proportion of the non-binding type bile acid and the conjugated bile acid in the serum and the feces was changed obviously.3.LD formula treatment increased the excretion of TG in the feces of DIO rats and reduced the abdominal fat accumulation.The metabolism may have the effect on decreasing the lipid levels in lever and serum.4.LD formula improved the proportion of bile acid in DIO rats to a certain extent and it may be possible to reverse the synthesis of bile and to excess excretion of the bile in DIO rats.5.LD formula depressed the expression of FXR-SHP,CYP8b1,NTCP and OATP of the liver uptake transporters were reduced by LD formula.Conclusion1.In TCM theory,the gallbladder regulates the balance of body intake and output via storing and excreting the bile.The imbalance of storing and purging in the viscera or the imbalance state of more storage while less excretion could be overweight,and more excretion while less storage could be thin.2.Obesity-prone rats induced by high-fat diet shows the decrease of synthesis of bile acid,the increase of excretion,and the amount of bile acid pool decreased in obese rats,which affected the body’s diarrhea in food and lipid,which showed that there was more and less diarrhea and weight gain in obese rats.Obesity-resistant rats increased the synthesis of bile acids,decreased the excretion of bile acids,inhibited the excessive accumulation of food and lipid,and promoted lipid excretion,thus maintaining the body weight and blood lipid.3.LD formula inhibits the expression of FXR-SHP,and increases the expression of CYP8B1 with the depression of NTCP,OATP in the liver to promoted the synthesis of bile acid.And it also regulates the profile of bile acid metabolism and improves the imbalance of storage and excretion of lipid to block body weight gain and reduce liver fat and blood lipid in DIO rats. |
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