| BackgroundCholecystectomy is the most commonly performed procedure for the surgical treatment of patients with gallbladder diseases.In particular,laparoscopic cholecystectomy(LC),which reduces surgical trauma and accelerates postoperative recovery,has been widely accepted by surgeons and patients.Previously,removal of the gallbladder was deemed to have no effects on the body given its function as just storage for bile acids(BAs);however,recent studies have reported that cholecystectomy can induce numerous metabolic changes including body weight,glucose,lipid,and energy.The underlying mechanism of metabolic changes after cholecystectomy has not been well elucidated.Currently,BAs have been demonstrated in changes to whole-body metabolism as signaling molecules by activating target receptors located in the intestine,liver,and fat.The most widely studied receptors are the farnesoid X receptor(FXR)and the membrane G protein-coupled BA receptors(GPBAR1/TGR5).BAs circulated faster by continuously secreting into the duodenum after cholecystectomy,and the serum level of BAs also changed in different degrees,thereby leading to continuous exposure to high concentrations of bile acids of intestines and liver.Type 2 diabetes mellitus(T2DM)is a complex whole-body metabolic abnormality that leads to a decrease in quality of life for patients and a heavy economic burden on society,macroscopically involving age,obesity,diets,and lifestyle,also genetic architecture,signaling pathways,inflammation,endothelial dysfunction and iron overload in microscopic.Moreover,insulin resistance and decreased glucose tolerance are also responsible for the increased glucose.To date,there is not a single approach to cure or even remit diabetes,a "cocktail therapy" is still the mainstream treatment.Therefore,a whole and in-depth understanding of pathogenesis and metabolic characteristics in diabetes are conductive to develop an effective treatment based on the evidence.BAs as signaling molecules could affect the metabolism of glucose and lipid,and to our knowledge,there have been few reports about metabolic changes in patients with T2DM after LC.Part 1.Effects of cholecystectomy on metabolism of glucose and lipid in patients with type 2 diabetes:a retrospective studyObjectiveTo explore the metabolic changes of glucose and lipid in patients with T2DM after laparoscopic cholecystectomy.MethodsClinical data of T2DM patients who underwent LC from January 2015 to January 2019 in our hospital were collected and followed up retrospectively.The pre-and postoperative changes of metabolism were analyzed in the total patients and each subgroup.ResultsA total of 75 T2DM patients(33 males and 42 females)were included in the study.As defined,19 patients(25.3%)were "under control" with regard to glucose metabolism after cholecystectomy,28 patients(37.3%)were considered "in remission",and 10 patients(13.3%)had an "improved" status.There was no significant difference in body mass index(P=0.556)or food intake(P=0.226)between the time before surgery and 12 months afterward.The levels of fasting plasma glucose(P=0.001),hemoglobin A1C(P<0.001),total cholesterol(P=0.024),low-density lipoprotein cholesterol(P=0.006),and lipoprotein a(P=0.037)decreased after surgery,whereas those of triglyceride(P=0.011),high-density lipoprotein cholesterol(P=0.022),apolipoprotein A1(P=0.002),and free fatty acid(P=0.032)increased.In subgroup analysis,differences in metabolic characteristics seemed to be more pronounced in the group of female,age≥60 years,BMI≥24,and non-hyperlipidemia.ConclusionsGlucose and lipid metabolism improved in T2DM patients after LC,it may be relate to the elevated level of bile acid.The metabolic changes are more pronounced in female,aged≥60 years,BMI≥24,and non-hyperlipidemia patients.Part 2.Changes of bile acids and energy expenditure after laparoscopic cholecystectomy in type 2 diabetes patients:a prospective studyObjectiveOur aims were to investigate changes of bile acids and resting energy expenditure(REE)in patients with T2DM after LC and the role in metabolic homeostasis.MethodsFrom December 2019 to October 2020,a total of 77 T2DM patients with gallbladder polyps were included in our study.Among them,40 patients who underwent LC were enrolled into the cholecystectomy group,37 patients who did not undergo LC were enrolled into the control group.Preoperative and 6-months postoperative demographic data,body weight,food intake,effects on diabetes control,and biomedical variables were recorded and compared.ResultsThe mean level of total bile acids(TBA)was higher than that in the control group(P=0.033)and increased significantly after LC compared to baseline(P=0.029).The REE level in the cholecystectomy group was higher than that in the control group(P=0.032)and increased compared to the baseline(P=0.011).The utilization of carbohydrates increased significantly after LC(P<0.001)while the utilization of fat decreased(P<0.001).The mean level of FBG(P=0.004),HbA1C(P<0.001)and HOMA-IR(P=0.045)decreased after LC,as defined,the total effectiveness rate was 45%.The mean level of total cholesterol(P=0.003)and low-density lipoprotein cholesterol significantly decreased(P=0.021),whereas the level of high-density lipoprotein cholesterol increased(P<0.001).ConclusionsThe level of REE and TBA increased after LC in patients with T2DM,the glucose and lipid metabolism partly improved.Trial registrationChinese Clinical Trial Registry,ChiCTR1900027823.Registered 30 November 2019,http://www.chictr.org.cn/index.aspx.Part 3.Metabolic improvement and possible mechanism after cholecystectomy in mice with type 2 diabetesObjectiveOur aim was to investigate the changes of glucose,lipid,bile acids and energy after cholecystectomy in mice with T2DM,and elucidate the potential mechanism of remission in T2DM.MethodsTwenty male mice with T2DM were randomly divided into cholecystectomy and sham groups.The gallbladder in the cholecystectomy group was gently removed through a small medial laparotomy.The sham operation involved the same incisions without removal of the gallbladder.The levels of fasting blood glucose(FBG),insulin,total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),free fatty acids(FFA),glucagon-like peptide-1(GLP-1),gastric inhibitory polypeptide(GIP),rest energy expenditure(REE)and total bile acids(TBA)were analyzed.After sacrifice,the expression levels of famesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5)and 7-alpha-hydroxylase(CYP7A1)in the liver,muscle and adipose tissue were examined.ResultsAlthough the two groups of mice were pair-fed,the body weights(P<0.001)and the levels of FBG(P<0.001)and insulin(P=0.013)in the cholecystectomy group significantly decreased 24 weeks after surgery.The intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test showed improvements in glucose tolerance(P=0.032)and insulin sensitivity(P=0.002),respectively,after cholecystectomy.The level of GLP-1 increased significantly(P=0.002),and there was no significant difference in the level of GIP between the two groups(P=0.15).The levels of TC(P<0.001)and LDL-C(P<0.001)were decreased,while the levels of TG(P=0.003),HDL-C(P<0.001),and FFA(P<0.001)were increased at the 24th postoperative week.Moreover,the serum TBA concentration in the cholecystectomy group was higher than that in the control group(P<0.001),also for the fecal TBA level(P=0.003),the expression of CYP7A1 mRNA(P=0.005)and protein(P=0.003)in live was upregulated.The REE level significantly increased 24 weeks after surgery(P=0.005).The expression of FXR in the liver(P=0.034),muscle(P=0.003)and adipose tissue(P=0.045)and that of TGR5 in the liver(P=0.024),muscle(P=0.026)and adipose tissue(P=0.004)were upregulated after surgery.The type 2 iodothyronine deiodinase(D2)expression also increased in adipose tissue(P=0.029)and gastrocnemius(P=0.015).ConclusionsIn mice with T2DM that underwent cholecystectomy,metabolism of glucose,lipid and energy were improved.Anabolism of bile acid in the liver enhanced and serum TBA levels were increased. |
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