Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with v...Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3a,MUC3b,MUC4,MUC5ac and MUC5b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20±1.50 vs.109.40±3.84 HU,P<0.0001).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3a,MUC3b,MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49±0.69 vs.10.23±0.54 ng/mL,P<0.05),in the body(14.54±0.94 vs.11.87±0.85 ng/mL,P<0.05)as well as in the neck(14.77±1.04 vs.10.85±0.72 ng/mL,P<0.05)of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r=0.569,P<0.05)in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.展开更多
Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understo...Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understood,so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones.The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors,among which genetic susceptibility,intestinal microflora disorders,impaired gallbladder motility,and immune disorders are important in the pathogenesis of cholesterol gallstones.This review focuses on recent advances in these mechanisms.We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones,which may be hot areas in the future.展开更多
with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbla...with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.展开更多
BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may pl...BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in pa- tients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2 mRNA was studi- ed in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-poly- merase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in pa- tients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.展开更多
BACKGROUND: The effect of 'intestinal transit' has become a new field of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain...BACKGROUND: The effect of 'intestinal transit' has become a new field of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain the relationship between impaired intestinal transit function and cholesterol gallstones. METHODS: A total of 64 hamsters were divided into 2 groups, experimental and control. Each was subdivided into 4 subgroups for sacrifice at different time. A high-cholesterol diet and a standard diet were fed to each group. The geometric center, which represents the intestinal transit function was calculated. RESULTS: The growth of all hamsters was normal. Cholesterol gallstones were found in 2 hamsters at the end of the 4th week. The geometric center values for the experimental and control groups were 2.3891 +/- 0.3923 vs. 2.7730 +/- 0.5283, at the end of week 3; 1.8148 +/- 0.4312 vs. 3.2294 +/- 1.1613 at week 4; 1.8451 +/- 0.3700 vs. 2.9075 +/- 0.3756 at week 5; and 1.8025 +/- 0.3413 vs. 3.0920 +/- 0.5622 at week 6. CONCLUSION: A high cholesterol diet can significantly reduce the intestinal transit function and facilitate the formation of cholesterol gallstones.展开更多
AIM:To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients. METHODS:The contraction forces of gallbladder smooth muscle stri...AIM:To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients. METHODS:The contraction forces of gallbladder smooth muscle strips from 28 patients with cholesterol gallstones treated with UDCA were compared with contraction forces from 14 untreated patients. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8). RESULTS:Although the contraction forces that developed in response to CCK-8 were higher in strips from specimens of UDCA treated patients compared to untreated patients,longer treatment periods (6-wk) caused more contraction responses than the short treatment period of 3-wk (F = 19.297,1.85 ± 0.22 g vs 1.70 ± 0.10 g,P < 0.01). Contraction forces developed with maximal stimulation with KCl in the 6-wk treatment group were also higher than contraction forces in the untreated group (F = 4.274,3.77 ± 0.45 g vs 3.30 ± 0.30 g,P < 0.05). CONCLUSION:Six-week UDCA treatment caused an increase in contractions of muscle strips from patients with cholesterol gallstones when compared to shorter treatment administration or controls. We suggest that extending UDCA treatment periods may cause more effective contractions in the gallbladder,and thereby increase the rate of response to treatment.展开更多
Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of un...Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.展开更多
IM To analyze serum bile acids and biliary lipids of patients with cholesterol gallstone(CS) and explore the relationship between deoxycholic acid (DCA) and CS disease.METHODS Analysis of bile acids in serum was do...IM To analyze serum bile acids and biliary lipids of patients with cholesterol gallstone(CS) and explore the relationship between deoxycholic acid (DCA) and CS disease.METHODS Analysis of bile acids in serum was done with gaschromatography in two groups: CS group (n=151) and control group (n=256). Serum bile acids and biliary lipids were also studied in 90 matched samples..RESULTS The serum DCA was 0955μmol/L±0078μmol/L in CS group, which was more than that of control group (0696μmol/L±0047μmol/L), P<001. The ratio of DCA/chenodeoxycholic acids (CDCA) was 176±030 in CS group, about two times that in control group (092±014). The mole percent of DCA in bile was positively related to cholesterol saturation index (CSI) (P<001) and the mole percent of CDCA in bile negatively to CSI (P=001). There was correlation between the mole percent of DCA, CDCA and cholic acid in bile and in serum.CONCLUSION It is suggested that DCA is lithogenic and the increased amount of DCA or the ratio of DCA/CDCA in serum may be one of the features of cholesterol gallstone patients.展开更多
Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incomplet...Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated.In addition to genetic predisposition and hepatic hypersecretion,the pathogenesis of cholelithiasis might involve the gastrointestinal(GI)microbiome,consisting of microorganisms and their metabolites.High-throughput sequencing studies have elucidated the role of bile,gallstones,and the fecal microbiome in cholelithiasis,associating microbiota dysbiosis with gallstone formation.The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways.This review examines the literature implicating the GI microbiome in cholelithiasis,specifically gallbladder stones,choledocholithiasis,and asymptomatic gallstones.We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.展开更多
AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD).METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two h...AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD).METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate)stratified by BMI was used to calculate the risk of GD.RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI ＜30. The selected variables in the model were HOMA-IR index with OR = 1.31, P= 0.02 and leptin higher than median with OR = 2.11, P= 0.05. In the stratum of BMI ≥30, we did not find a useful model.CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.展开更多
We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of ...We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% （w/w） butter fat, 1% （w/w） cholesterol, and 0.5% （w/w） cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Tr~ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxra, Rxr, and Cyp7al were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxra and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.展开更多
基金the National Natural Science Foundation of China(81870433)the International Cooperation Project of Zhejiang Province Public Technology Research Program(LGJ18H030001).
文摘Background:Cholesterol gallstones account for over 80%of gallstones,and the pathogenesis of gallstone formation involves genetic and environmental factors.However,data on the evolution of cholesterol gallstones with various densities are limited.This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods:Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones.The relative abundance of microbiota in gallbladder tissues was detected.Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1,MUC2,MUC3a,MUC3b,MUC4,MUC5ac and MUC5b in gallbladder tissues and bile.The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results:A total of 23 patients with gallbladder stones were included.The density of gallstones in the isodense group was significantly lower than that of the calcified group(34.20±1.50 vs.109.40±3.84 HU,P<0.0001).Compared to the isodense group,the calcified group showed a higher abundance of gram-positive bacteria at the fundus,in the body and neck of gallbladder tissues.The concentrations of MUC1,MUC2,MUC3a,MUC3b,MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups,while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus(15.49±0.69 vs.10.23±0.54 ng/mL,P<0.05),in the body(14.54±0.94 vs.11.87±0.85 ng/mL,P<0.05)as well as in the neck(14.77±1.04 vs.10.85±0.72 ng/mL,P<0.05)of gallbladder tissues.Moreover,the abundance of bacteria was positively correlated with the expression of MUC4(r=0.569,P<0.05)in the calcified group.Conclusions:This study showed the potential clinical relevance among biliary microbiota,mucins and calcified gallstones in patients with gallstones.Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones.
基金Supported by the Wu Jiping Medical Foundation,No.320.6750.18396Nantong“14th Five-Year”Science and Education to Strengthen Health Project,General Surgery Medical Key Discipline.
文摘Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understood,so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones.The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors,among which genetic susceptibility,intestinal microflora disorders,impaired gallbladder motility,and immune disorders are important in the pathogenesis of cholesterol gallstones.This review focuses on recent advances in these mechanisms.We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones,which may be hot areas in the future.
基金National Natural Science Foundation of China,No.81000183and Natural Science Foundation of Liaoning Province,No.20180550125.
文摘with a complex and multifactorial etiology.Declined gallbladder motility reportedly contributes to CG pathogenesis.Furthermore,interstitial Cajal-like cells(ICLCs)are reportedly present in human and guinea pig gallbladder tissue.ICLCs potentially contribute to the regulation of gallbladder motility,and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis.This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.
基金This study was supported by a grant from the Health Bureau of Tianjin, China(No. 00kyzd8).
文摘BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2 ( SCP2 ) participates in choles- terol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in pa- tients with cholesterol gallstone and those patients with non-cholesterol gallstone. METHODS: The expression of liver SCP2 mRNA was studi- ed in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-poly- merase chain reaction (RT-PCR). RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone. CONCLUSION: The SCP2 gene was overexpressed in pa- tients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.
文摘BACKGROUND: The effect of 'intestinal transit' has become a new field of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain the relationship between impaired intestinal transit function and cholesterol gallstones. METHODS: A total of 64 hamsters were divided into 2 groups, experimental and control. Each was subdivided into 4 subgroups for sacrifice at different time. A high-cholesterol diet and a standard diet were fed to each group. The geometric center, which represents the intestinal transit function was calculated. RESULTS: The growth of all hamsters was normal. Cholesterol gallstones were found in 2 hamsters at the end of the 4th week. The geometric center values for the experimental and control groups were 2.3891 +/- 0.3923 vs. 2.7730 +/- 0.5283, at the end of week 3; 1.8148 +/- 0.4312 vs. 3.2294 +/- 1.1613 at week 4; 1.8451 +/- 0.3700 vs. 2.9075 +/- 0.3756 at week 5; and 1.8025 +/- 0.3413 vs. 3.0920 +/- 0.5622 at week 6. CONCLUSION: A high cholesterol diet can significantly reduce the intestinal transit function and facilitate the formation of cholesterol gallstones.
文摘AIM:To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients. METHODS:The contraction forces of gallbladder smooth muscle strips from 28 patients with cholesterol gallstones treated with UDCA were compared with contraction forces from 14 untreated patients. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8). RESULTS:Although the contraction forces that developed in response to CCK-8 were higher in strips from specimens of UDCA treated patients compared to untreated patients,longer treatment periods (6-wk) caused more contraction responses than the short treatment period of 3-wk (F = 19.297,1.85 ± 0.22 g vs 1.70 ± 0.10 g,P < 0.01). Contraction forces developed with maximal stimulation with KCl in the 6-wk treatment group were also higher than contraction forces in the untreated group (F = 4.274,3.77 ± 0.45 g vs 3.30 ± 0.30 g,P < 0.05). CONCLUSION:Six-week UDCA treatment caused an increase in contractions of muscle strips from patients with cholesterol gallstones when compared to shorter treatment administration or controls. We suggest that extending UDCA treatment periods may cause more effective contractions in the gallbladder,and thereby increase the rate of response to treatment.
文摘Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.
文摘IM To analyze serum bile acids and biliary lipids of patients with cholesterol gallstone(CS) and explore the relationship between deoxycholic acid (DCA) and CS disease.METHODS Analysis of bile acids in serum was done with gaschromatography in two groups: CS group (n=151) and control group (n=256). Serum bile acids and biliary lipids were also studied in 90 matched samples..RESULTS The serum DCA was 0955μmol/L±0078μmol/L in CS group, which was more than that of control group (0696μmol/L±0047μmol/L), P<001. The ratio of DCA/chenodeoxycholic acids (CDCA) was 176±030 in CS group, about two times that in control group (092±014). The mole percent of DCA in bile was positively related to cholesterol saturation index (CSI) (P<001) and the mole percent of CDCA in bile negatively to CSI (P=001). There was correlation between the mole percent of DCA, CDCA and cholic acid in bile and in serum.CONCLUSION It is suggested that DCA is lithogenic and the increased amount of DCA or the ratio of DCA/CDCA in serum may be one of the features of cholesterol gallstone patients.
文摘Cholelithiasis is a common digestive disease affecting 10%to 15%of adults.It imposes significant global health and financial burdens.However,the pathogenesis of cholelithiasis involves several factors and is incompletely elucidated.In addition to genetic predisposition and hepatic hypersecretion,the pathogenesis of cholelithiasis might involve the gastrointestinal(GI)microbiome,consisting of microorganisms and their metabolites.High-throughput sequencing studies have elucidated the role of bile,gallstones,and the fecal microbiome in cholelithiasis,associating microbiota dysbiosis with gallstone formation.The GI microbiome may drive cholelithogenesis by regulating bile acid metabolism and related signaling pathways.This review examines the literature implicating the GI microbiome in cholelithiasis,specifically gallbladder stones,choledocholithiasis,and asymptomatic gallstones.We also discuss alterations of the GI microbiome and its influence on cholelithogenesis.
基金Supported by the National Council of Science and Technology of Mexico (CONACYT)The Ministry of Health (SSA), Mexico project No. M0059-M9602 (NM-S and MU)
文摘AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD).METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate)stratified by BMI was used to calculate the risk of GD.RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI ＜30. The selected variables in the model were HOMA-IR index with OR = 1.31, P= 0.02 and leptin higher than median with OR = 2.11, P= 0.05. In the stratum of BMI ≥30, we did not find a useful model.CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.
基金Project supported by the National Natural Science Foundation of China(No.81001084)
文摘We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% （w/w） butter fat, 1% （w/w） cholesterol, and 0.5% （w/w） cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Tr~ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxra, Rxr, and Cyp7al were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxra and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.
