title: Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: A randomized, controlled, crossover feeding study. Increased glycine-amidated hyocholic acid correlates to improved early weight loss after sleeve gastrectomy Comparison of Changes in Lipid Profile after Bilio-intestinal Bypass and Gastric Banding in Patients with Morbid Obesity Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation Effects of Surgical and Dietary Weight Loss Therapy for Obesity on Gut Microbiota Composition and Nutrient Absorption Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial. Enhanced fasting and post-prandial plasma bile acid responses after Roux-en-Y gastric bypass surgery Bile acid profiles over 5 years after gastric bypass and duodenal switch: results from a randomized clinical trial. Bile acid malabsorption after jejunoileal bypass is less compensated for with a 1:3 than with a 3:1 jejunoileal ratio. Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss Cholesterol saturation of bile after jejunoileal bypass increases more with a 1:3 than with a 3:1 jejunoileal ratio. Bile acids synthesis decreases after laparoscopic sleeve gastrectomy. Effect of orlistat on fecal fat, fecal biliary acids, and colonic cell proliferation in obese subjects. Serum levels and clearance of bile acids are unaffected by jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids.
abstract: OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively . However , the effects of diets high in whole versus refined grains on circulating bile acids , which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor ( FXR ) and G protein-coupled bile acid receptor 1 ( TGR5 ) , have not been studied . MATERIAL S AND METHODS We conducted a secondary analysis from a r and omized controlled crossover feeding trial ( NCT00622661 ) in 80 healthy adults ( 40 women/40 men , age 18 - 45 years ) from the greater Seattle Area , half of which were normal weight ( BMI 18.5 - 25.0 kg/m2 ) and half overweight to obese ( BMI 28.0 - 39.9 kg/m2 ) . Participants consumed two four-week controlled diets in r and omized order : 1 ) a whole grain diet ( WG diet ) , design ed to be low in glycemic load ( GL ) , high in whole grains , legumes , and fruits and vegetables , and 2 ) a refined grain diet ( RG diet ) , design ed to be high GL , high in refined grains and added sugars , separated by a four-week washout period . Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography t and em mass spectrometry . Concentrations of glucose , insulin , and CRP were measured in fasting serum . Linear mixed models were used to test the effects of diet on bile acid concentrations , and determine the association between plasma bile acid concentrations and HOMA-IR and CRP . Benjamini-Hochberg false discovery rate ( FDR ) < 0.05 was used to control for multiple testing . RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis . Taurolithocholic acid ( TLCA ) , taurocholic acid ( TCA ) and glycocholic acid ( GCA ) were statistically significantly higher after the WG compared to the RG diet ( FDR < 0.05 ) . There were no significant differences by BMI or sex . When evaluating the association of bile acids and HOMA-IR , GCA , taurochenodeoxycholic acid , ursodeoxycholic acid ( UDCA ) , 5β‑cholanic acid‑3β,12α‑diol , 5‑cholanic acid‑3β‑ol , and glycodeoxycholic acid ( GDCA ) were statistically significantly positively associated with HOMA-IR individually , and as a group , total , 12α‑hydroxylated , primary and secondary bile acids were also significant ( FDR < 0.05 ) . When stratifying by BMI , chenodeoxycholic acid ( CDCA ) , cholic acid ( CA ) , UDCA , 5β-cholanic acid-3β , deoxycholic acid , and total , 12α-hydroxylated , primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals ( FDR < 0.05 ) . When stratifying by sex , GCA , CDCA , TCA , CA , UDCA , GDCA , glycolithocholic acid ( GLCA ) , total , primary , 12α‑hydroxylated , and glycine-conjugated bile acids were significantly associated with HOMA-IR among women , and CDCA , GDCA , and GLCA were significantly associated among men ( FDR < 0.05 ) . There were no significant associations between bile acids and CRP . CONCLUSIONS Diets with comparable macronutrient and energy composition , but differing in carbohydrate source , affected fasting plasma bile acids differently . Specifically , a diet characterized by whole grains , legumes , and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA , TCA and GCA , lig and s for FXR and TGR5 , which may have beneficial effects on glucose homeostasis Background Bile acids ( BAs ) are post-pr and ial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure . Total and glycine-ami date d BAs increase after sleeve gastrectomy ( SG ) and correlate to improved metabolic disease . No specific bile acid subtype has been shown conclusively to mediate the weight loss effect . Therefore , the objective of this study was to prospect ively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response . Methods Patients were prospect ively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity . Primary and secondary plasma bile acids and their ami date d ( glycine , G- , or taurine , T- ) subtypes were measured at fasting , 30 and 60 min after a liquid meal performed pre-op , and at 6 and 12 weeks post-op . Area under the curve ( AUC ) was calculated for the hour meal test for each bile acid subtype . BAs that were significantly increased post-op were correlated to body mass index ( BMI ) loss . Results Total BA AUC was significantly increased at 6 ( p < 0.01 ) and 12 weeks post-op ( p < 0.01 ) compared to pre-operative values . The increase in total BA AUC was due to a statistically significant increase in G-BAs . Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op . Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss ( p = 0.03 ) . Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 ( p = 0.05 ) and 12 weeks ( p = 0.006 ) . Conclusions SG induced an early and persistent post-pr and ial surge in multiple bile acid subtypes . Increased G-hyocholic consistently correlated with greater early BMI loss . This study provides evidence for a role of BAs in the surgical weight loss response after SG Background : The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery . Methods : We prospect ively investigated the effects of the bilio-intestinal bypass ( BI-bypass ) with a wide cholecysto-jejunal anastomosis and of adjustable gastric b and ing ( AGB ) on blood lipid concentrations in obese patients . To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass , daily fecal sterol excretion was measured by gas-liquid chromatography ( GLC ) . Results : At 1 year after BI-bypass compared to baseline , the hypercholesterolemic ( n=18 ) and the normocholesterolemic ( n=19 ) patients significantly reduced total ( −38 % and −27 % , respectively ) , LDL ( −47 % and −24 % , respectively ) and HDL ( −11 % and −13 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −25 % and −13 % , respectively ) . At 1 year after AGB , the total / HDL cholesterol ratio was significantly decreased ( −11 % ) compared to baseline in hypercholesterolemic ( n=12 ) but not in normocholesterolemic ( n=6 ) patients , while total and LDL cholesterol were not affected in both groups . At 3 years after BI-bypass compared to baseline , the hypercholesterolemic ( n=9 ) and the normocholesterolemic ( n=11 ) patients significantly reduced total ( −43 % and −28 % , respectively ) and LDL ( −53 % and −29 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −38 % and −21 % , respectively ) . The BI-bypass induced a significant ( P < 0.005 ; n=7 ) 6-fold increase in mean fecal cholesterol output . Conclusions : The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output . BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia Summary Bariatric surgery is currently the most effective procedure for the treatment of obesity . Given the role of the gut microbiota in regulating host metabolism and adiposity , we investigated the long-term effects of bariatric surgery on the microbiome of patients r and omized to Roux-en-Y gastric bypass or vertical b and ed gastroplasty and matched for weight and fat mass loss . The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and result ed in altered levels of fecal and circulating metabolites compared with obese controls . By colonizing germ-free mice with stools from the patients , we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice . These mice also had a lower respiratory quotient , indicating decreased utilization of carbohydrates as fuel . Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction . Laparoscopic sleeve gastrectomy ( LSG ) , a surgical intervention for obesity , is classified as predominantly restrictive procedure . In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects ( n = 5 per group ) demonstrating identical weight loss during a follow-up period of six months . For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics . The energy-reabsorbing potential of the gut microbiota decreased following LSG , indicated by the Bacteroidetes/Firmicutes ratio , but increased during diet . Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups . No alteration of faecal butyrate was observed , but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention . LSG result ed in enhanced faecal excretion of nonesterified fatty acids and bile acids .  LSG , but not dietetic restriction , improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype . Moreover , LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation . This trial is registered with Clinical Trials.gov NCT01344525 OBJECTIVE Increased delivery of bile acid salts ( BA ) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery . To further eluci date a potential role of BA in the secretion of GLP-1 and PYY , we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospect i ve , r and omized 1-year trial . DESIGN AND METHODS Patients  received a st and ard test meal and blood was collected before and after eating , prior to , and 1 week , 3 months , and 12 months after surgery . RESULTS Pre-surgery , basal BA concentrations were significantly lower in bariatric patients than in healthy controls . One year post-surgery , bariatric patients expressed variably increased BA concentrations ( gastric bypass patients ∼2 fold increase , P ≤ 0.05 ) . However , whereas in both patient groups , marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery , changes in plasma BA followed a different pattern : basal and postpr and ial plasma BA concentrations increased much slower , more progressively with significant increases only 1-year post-surgery . CONCLUSIONS Based on these findings , BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients Abstract Objective . Exogenous bile acid ( BA ) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass ( RYGB ) surgery . Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB , with subsequent increased fasting plasma BAs . The study assessed fasting and post-pr and ial plasma BA response before and 15 months after RYGB . Material and methods . The prospect i ve study recruited 63 obese individuals ( 43 females ) , aged 43 ( 36–56 ) [ median ( IQR ) ] years .  Blood sample s were collected before and every 30 min for 120 min after a st and ard 400 kcal meal .  Fasting and post-pr and ial plasma BAs , glucagons like peptide-1 ( GLP-1 ) , –tyrosine ( PYY ) , fasting C-reactive protein ( CRP ) , glucose and insulin were measured and homeostasis model assessment -insulin resistance ( HOMA-IR ) was calculated . Results . Following RYGB , body mass index , CRP , fasting glucose and HOMA-IR decreased ; 43.7 ( 39.3–49.2 ) kg/m2 to 29.2 ( 25.1–35.0 ) kg/m2 , 7.9 ( 4.1–11.9 ) mg/L to 0.4 ( 0.2–1.0 ) mg/L , 5.5 ( 5.0–6.0 ) mmol/L to 4.6 ( 4.3–4.9 ) mmol/L and 5.9 ( 3.5–9.2 ) to 1.7 ( 1.1–2.2 ) , respectively , all P < 0.001 . Fasting total BAs , GLP-1 and PYY increased after RYGB ; 1.69 ( 0.70–2.56 ) µmol/L to 2.43 ( 1.23–3.82 ) µmol/L ( P = 0.02 ) , 6.8 ( 1.5–15.3 ) pmol/L to 17.1 ( 12.6–23.9 ) pmol/L ( P < 0.001 ) and 4.0 ( 1.0–7.1 ) pmol/L to 15.2 ( 10.0–28.3 ) pmol/L ( P < 0.001 ) , respectively . The area under the curve for post-pr and ial total BAs , total glycine-conjugated BAs , GLP-1 and PYY were greater after RYGB ; 486 ( 312–732 ) µmol/L/min versus 1012 ( 684–1921 ) µmol/L/min , 315 ( 221–466 ) µmol/L/min versus 686 ( 424–877 ) µmol/L/min , 3679 ( 3162–4537 ) pmol/L/min versus 5347 ( 4727–5781 ) pmol/L/min and 1887 ( 1423–2092 ) pmol/L/min versus 3296 ( 2534–3834 ) pmol/L/min , respectively , all P < 0.0001 . Conclusion . Weight loss following RYGB is associated with an increase in post-pr and ial plasma BA response due to larger amounts of glycine-conjugated BAs . This suggests up regulation of BA production and conjugation after RYGB BACKGROUND Bile acids have been proposed as key mediators of the metabolic effects after bariatric surgery . Currently no reports on bile acid profiles after duodenal switch exist , and long-term data after gastric bypass are lacking . OBJECTIVE To investigate bile acid profiles up to 5 years after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch and to explore the relationship among bile acids and weight loss , lipid profile , and glucose metabolism . SETTING S Two Sc and inavian University Hospitals . METHODS We present data from a r and omized clinical trial of 60 patients with body mass index 50 - 60 kg/m2 operated with gastric bypass or duodenal switch .  Repeated measurements of total and individual bile acids from fasting serum during 5 years after surgery were performed . RESULTS Mean concentrations of total bile acids increased from 2.3 µmol/L ( 95 % confidence interval [ CI ] , -.1 to 4.7 ) at baseline to 5.9 µmol/L ( 3.5 - 8.3 ) 5 years after gastric bypass and from 1.0 µmol/L ( 95 % CI , -1.4 to 3.5 ) to 9.5 µmol/L ( 95 % CI , 7.1 - 11.9 ) after duodenal switch ; mean between-group difference was -4.8 µmol/L ( 95 % CI , -9.3 to -.3 ) , P = .036 . Mean concentrations of primary bile acids increased more after duodenal switch , whereas secondary bile acids increased proportionally across the groups . Higher levels of total bile acids at 5 years were associated with lower body mass index , greater weight loss , and lower total cholesterol . CONCLUSIONS Total bile acid concentrations increased substantially over 5 years after both gastric bypass and duodenal switch , with greater increases in total and primary bile acids after duodenal switch . ( Surg Obes Relat Dis 2017;0:000 - 000 . ) © 2017 American Society for Metabolic and Bariatric Surgery . All rights reserved A previous study surprisingly showed that after jejunoileal bypass a ratio of 1:3 compared with 3:1 between the jejunal and ileal segment left in continuity result ed in a smaller synthesis rate , pool size , and postcibal jejunal levels of bile acids . These findings are reevaluated in the present study of 34 patients who either were waiting for or 3 , 9 , or 15 months earlier , had undergone bypass surgery with a 3:1 or 1:3 jejunoileal ratio . Compared with 3:1 bypass , the 1:3 bypass result ed in ( i ) greater reduction of the fasting bile acid pool , significant for chenodeoxycholic acid but not for cholic adic , ( ii ) less increase in synthesis rate of both bile acids , ( iii ) less decrease in relative content of taurine-conjugated bile acids in bile , and ( iv ) equal reduction of postcibal levels of bile acids in jejunum . We conclude that the increase in synthesis of bile acids compensates insufficiently for the excess fecal loss ; the lower synthesis rate after bypass with a short jejunum relative to ileum in function may be due to an impaired stumulation of bile acid synthesis , the mechanism of which is unexplained OBJECTIVES : Orlistat , an intestinal lipase inhibitor , has recently been approved by the US Food and Drug Administration for treatment of obesity . The effects of orlistat on hepatobiliary function have not been previously defined . A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet . METHODS : A total of 23 obese ( BMI 30–41 kg/m2 ) subjects were r and omized to a double blind t.i.d . treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet ( 1200–1500 kcal/day ) . The study was design ed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat .  Cholesterol saturation , bile composition , and gallbladder motility were measured . RESULTS : At the end of the treatment period , mean weight loss of 3.8 kg was achieved in the orlistat group ( vs 2.3 kg with placebo , p = NS ) . Total bile acid concentration decreased significantly with placebo ( –18.57 ± 6.99 mmol/L ; 95 % CI = –32.26 to –4.87 ) , but not with orlistat . Biliary phospholipid concentration decreased significantly with placebo ( −4.38 ± 1.91 mmol/L ; 95 % CI = –8.13 to –0.64 ) but not with orlistat . Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups . Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group . CONCLUSIONS : Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids . Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function . We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat Previous suggested , surprisingly , that after jejunoileal bypass surgery the lithogenicity of the bile , assessed by its cholesterol saturation and rate of gallstone formation , increases more with a 1:3 than with a 3:1 jejunoileal ratio of the functioning segment . The present study re-evaluates this by examining fasting bile sample s drawn from duodenum after cholecystokinin stimulation in 34 obese patients without gallstones , who either were waiting for or had had bypass surgery , with a 1:3 or 3:1 jejunoileal ratio , 3,9 , or 15 months earlier . In all groups , the cholesterol content exceeded the solubilizing capacity of the bile as determined on the basis of total lipid concentration and content of phospholipid relative to bile acids . The cholesterol supersaturation increased with bypass surgery as such , increased more with a 1:3 than with a 3:1 jejunoileal ratio , decreased with time after surgery , and reached the preoperative level at 15 months . Assuming a total lipid concentration of 10 g/dl in the bile did not change this pattern . Our results indicate that during the period of weight loss after bypass surgery the lithogenicity of gallbladder bile increases more with a 1:3 than with a 3:1 jejunoileal ratio BACKGROUND Bariatric surgery is the most effective treatment alternative in morbid obesity . The mechanisms contributing to these benefits remain poorly understood . Bile acids ( BAs ) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure . Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy ( SG ) . OBJECTIVES The aim of this study was to evaluate the effect of SG on BA synthesis . SETTING University Hospital . Santiago , Chile . METHODS Obese patients were evaluated before and after SG ( 1 , 3 , 6 , and 12 months ) . BA synthesis was evaluated through the serum marker , 7 α-hydroxy-4-cholesten-3-one ( C4 ) . Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with t and em mass spectrometry detection ( HPLC-MS/MS ) . RESULTS From June 2013 to January 2014 , 19 patients ( age 37.6±7.8 years ; BMI 35.8±3.5 kg/m(2 ) ; 79 % female ) were included in this study . Mean weight loss at 1 , 3 , 6 , and 12 months was 11.3 , 17.5 , 23.6 , and 25.4 kg , respectively , equivalent to 11.8 , 18.6 , 24.8 , and 26.9 of total body water percentage ( % TBW ) ( P<.0001 ) , respectively and 43.2 , 68.2 , 91 , and 98.8 of percentage of excess weight loss ( % EWL ) , respectively ( P<.001 ) . Serum C4 levels at baseline , 1 , 3 , 6 , and 12 months were 23.4±21.1 , 4.9±8.2 , 8.7±12.1 , 13.8±12.9 , and 18.8±16.8 ng/mL ( P<.0001 ) , respectively . Fibroblast growth factor 19 ( FGF19 ) levels at baseline , 1 , 3 , 6 , and 12 months were 71±33.3 , 130.5±66.2 , 117.8±57.2 , 134.6±91.7 , and 124.3±85.9 pg/mL ( P = .019 ) , respectively . CONCLUSION Serum levels of C4 decrease after SG , indicating a reduction in the synthesis of BA . FGF19 may play a role in decreasing BA synthesis . Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis BACKGROUND & AIMS Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity . Because of orlistat 's mode of action , increased fecal fat is presented to the colonic mucosa , and fecal bile acid and free fatty acid composition may be altered during treatment . Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation . METHODS Twenty-four obese ( body mass index , 30 - 40 kg/m2 ) but otherwise healthy male and female subjects were enrolled in a single-center , r and omized , double-blind , placebo-controlled  , parallel-group study . Participants were hospitalized during days 1 - 3 and 33 - 42 of treatment and were treated as out patients for the remaining days . RESULTS Treatment with orlistat for 6 weeks result ed in significantly greater increases in fecal weight , total fecal fat , and fecal free fatty acids than placebo .  Total fecal bile acid amounts decreased slightly with orlistat , and increased significantly with placebo treatment ( P < .05 between-group difference ) . Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices ( 5-bromo-2-deoxyuridine , whole crypt mitotic count , and proliferating cell nuclear antigen ) . CONCLUSIONS Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation , a putative biomarker of colon cancer risk Jejunoileal bypass may impair  liver function .  The hypothesis of the present study was that this may depend on the jejunoileal ratio of the segment left in continuity in a manner that affects the transport of bile acids from blood to bile . We investigated five extremely obese patients before and 29 patients 3 , 9 and 15 months after bypass surgery with a 3:1 or 1:3 jejunoileal ratio of the functioning segment .  Routine liver function tests , plasma disappearance rate of intravenously administered 3H-cholic acid and 14C-24-chenodeoxycholic acid , and fasting and postpr and ial serum concentrations of total 3-alpha-hydroxy bile acids showed no appreciable significant relationship with bypass surgery as such , time after surgery , or the jejunoileal ratio of the functioning segment CONTEXT It has been hypothesized that increased plasma bile acids ( BAs ) contribute to metabolic improvements after Roux-en-Y gastric bypass ( RYGB ) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones . OBJECTIVE The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis ( insulin secretion and sensitivity ) and energy metabolism ( resting energy expenditure and thyroid hormone axis ) . DESIGN , PARTICIPANTS , INTERVENTION , AND MAIN OUTCOME MEASURE : Eighteen extremely obese subjects were studied before and after 20 % weight loss , induced by either laparoscopic adjustable gastric b and ing ( LAGB ) ( n = 10 ) or RYGB surgery ( n = 8) . RESULTS Plasma BAs more than doubled after RYGB [ fasting : 1.08 ( 0.26 - 1.42 ) to 2.28 ( 1.59 - 3.28 ) μmol/L , P = .03 ; postpr and ial : 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L , P = .01 ] but were either lower or did not change after LAGB [ fasting : 1.80 ( 1.49 - 2.19 ) to 0.92 ( 0.73 - 1.15 ) μmol/L , P = .02 ; postpr and ial : 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L , P = .14 ] . Skeletal muscle expression of TGR5 targets , Kir6.2 and cyclooxygenase IV , increased after RYGB but not LAGB . Surgery-induced changes in BAs were associated with increased peak postpr and ial plasma glucagon-like peptide-1 ( r(2 ) = 0.509 , P = .001 ) and decreased serum TSH ( r(2 ) = 0.562 , P < .001 ) but did not correlate with the change in insulin response to a meal ( r(2 ) = 0.013 , P = .658 ) , insulin sensitivity ( assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure ) ( r(2 ) = 0.001 , P = .995 ) , or resting energy expenditure ( r(2 ) = 0.004 , P = .807 ) . CONCLUSIONS Compared with LAGB , RYGB increases circulating BAs and TGR5 signaling , but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism
target: Circulating fasting total BA was not associated with obesity .
  FGF19 was inversely and faecal BA excretion was positively associated with obesity .
  Roux-en-Y gastric bypass ( RYGB ) and sleeve gastrectomy ( SG )  modulated BA metabolism , ie , increased BA and FGF19 .
  Our results indicate that BA metabolism is altered in obesity .
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