human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Gastric bypass leads to the remission of  type 2 diabetes  independently of weight loss . Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation . We prospect ively studied 12 patients undergoing gastric bypass and six patients undergoing gastric b and ing over a 6-wk period . Plasma fibroblast growth factor (FGF)19 , stimulated by bile acid absorption in the terminal ileum , and plasma bile acids were measured . In canine and rodent models , we investigated changes in the gut hormone response after altered bile flow . FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric b and ing . In the canine model , both food and bile , on their own , stimulated satiety gut hormone responses . However , when combined , the response was doubled . In rats , drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response , reduced food intake , and lower body weight . In conclusion , after gastric bypass , bile flow is altered , leading to increased plasma bile acids , FGF19 , incretin . and satiety gut hormone concentrations . Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes CONTEXT Obstructive sleep apnea ( OSA ) is strongly related to obesity . Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA . OBJECTIVE To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 60 obese patients ( body mass index : > 35 and < 55 ) with recently diagnosed ( < 6 months ) OSA and an apnea-hypopnea index ( AHI ) of 20 events/hour or more . These patients had been prescribed continuous positive airway pressure ( CPAP )  therapy to manage OSA and were identified via accredited community sleep clinics . The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical research ers in Melbourne , Australia . Patients with obesity hypoventilation syndrome , previous bariatric surgery , contraindications to bariatric surgery , or significant cardiopulmonary , neurological , vascular , gastrointestinal , or neoplastic disease were excluded . INTERVENTIONS Patients were r and omized to a conventional weight loss program that included regular consultations with a dietitian and physician , and the use of very low-calorie diets as necessary ( n = 30 ) or to bariatric surgery ( laparoscopic adjustable gastric b and ing ; n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to r and omization . Secondary outcomes were changes in weight , CPAP adherence , and functional status . RESULTS Patients lost a mean of 5.1 kg ( 95 % CI , 0.8 to 9.3 kg ) in the conventional weight loss program compared with 27.8 kg ( 95 % CI , 20.9 to 34.7 kg ) in the bariatric surgery group ( P < .001 ) . The AHI decreased by 14.0 events/hour ( 95 % CI , 3.3 to 24.6 events/hour ) in the conventional weight loss group and by 25.5 events/hour ( 95 % CI , 14.2 to 36.7 events/hour ) in the bariatric surgery group . The between-group difference was -11.5 events/hour ( 95 % CI , -28.3 to 5.3 events/hour ; P = .18 ) . CPAP adherence did not differ between the groups . The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score ( mean , 9.3 [ 95 % CI , 0.5 to 18.0 ] ; P = .04 ) . CONCLUSION Among a group of obese patients with OSA , the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss . TRIAL REGISTRATION anzctr.org Identifier : 12605000161628 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 Objective Our objective was to investigate the role of bile acids in  hepatic steatosis reduction after vertical sleeve gastrectomy ( VSG ) . Design and Methods  High fat diet ( HFD ) induced obese C57Bl/6 mice were r and omized to : VSG , Sham operation ( Sham ) , Sham operation with pair feeding to VSG ( Sham-PF ) , or non-surgical controls ( Naïve ) . All mice were on HFD until sacrifice . Mice were observed post-surgery and data for body weight , body composition , metabolic parameters , serum bile acid level and composition were collected . Further hepatic gene expression by RNAseq and RT-PCR analysis was assessed . Results VSG and Sham-PF mice lost equal weight post-surgery while VSG mice had the lowest hepatic triglyceride content at sacrifice . The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss . Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid . These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes . Conclusion VSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone . VSG surgery increases serum bile acids that correlate with weight lost post-surgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis The physiological role of glucagon-like peptide-1 7 - 36 amide ( GLP-1 7 - 36 ) in man was investigated . GLP-1 7 - 36-like immunoreactivity was found in the human bowel ; its circulating level rose after oral glucose and after a test breakfast . When it was infused into seven volunteers at a rate to mimic its postpr and ial plasma concentration in the fasting state , plasma insulin levels rose significantly and glucose and glucagon concentrations fell . During an intravenous glucose load , it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations , compared with a control saline infusion , even inducing postinfusion reactive hypoglycaemia . By comparison , infusion of glucose-dependent insulinotropic peptide ( GIP ) to physiological levels was less effective in stimulating insulin release . These observations suggest that GLP-1 7 - 36 is a physiological incretin and that it is more powerful than GIP . The observation of greatly increased postpr and ial plasma GLP-1 7 - 36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder 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 Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome . Changes in intestinal and hepatic physiology after ileal interposition ( transposition ) surgery ( IIS )  are not well understood . Our aim was to eluci date the adaptation of the interposed ileum , which we hypothesized , would lead to early bile acid reabsorption in the interposed ileum , thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments . Rats with diet-induced obesity were r and omized to IIS  , with 10 cm of ileum repositioned distal to the duodenum , or sham surgery . A subgroup of sham rats was pair-fed to IIS rats . Physiological parameters were measured until 6 wk postsurgery . IIS rats ate less and lost more weight for the first 2 wk postsurgery . At study completion , body weights were not different , but IIS rats had reversed components of the metabolic syndrome . The interposed ileal segment adapted to a more jejunum-like villi length , mucosal surface area , and GATA4/ILBP mRNA . The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi . IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum , suggesting an early and efficient reabsorption of primary bile acids . IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss . There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR , SHP , or NTCP expression . IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling . There is early reabsorption of primary bile acids despite selective " jejunization " of the interposed ileal segment . Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery 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  
    Output:
    
agent
The findings support the effects of BAs on satiety , lipid and cholesterol metabolism , incretins and glucose homoeostasis , energy metabolism , gut microbiota and endoplasmic reticulum stress following bariatric surgery .
Many of these metabolic effects are modulated through the BA receptors FXR and TGR5 .
We also explore a possible link between BAs and carcinogenesis following bariatric surgery .
Conclusions : Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms .
BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Gastric bypass leads to the remission of  type 2 diabetes  independently of weight loss . Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation . We prospect ively studied 12 patients undergoing gastric bypass and six patients undergoing gastric b and ing over a 6-wk period . Plasma fibroblast growth factor (FGF)19 , stimulated by bile acid absorption in the terminal ileum , and plasma bile acids were measured . In canine and rodent models , we investigated changes in the gut hormone response after altered bile flow . FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric b and ing . In the canine model , both food and bile , on their own , stimulated satiety gut hormone responses . However , when combined , the response was doubled . In rats , drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response , reduced food intake , and lower body weight . In conclusion , after gastric bypass , bile flow is altered , leading to increased plasma bile acids , FGF19 , incretin . and satiety gut hormone concentrations . Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes CONTEXT Obstructive sleep apnea ( OSA ) is strongly related to obesity . Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA . OBJECTIVE To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 60 obese patients ( body mass index : > 35 and < 55 ) with recently diagnosed ( < 6 months ) OSA and an apnea-hypopnea index ( AHI ) of 20 events/hour or more . These patients had been prescribed continuous positive airway pressure ( CPAP )  therapy to manage OSA and were identified via accredited community sleep clinics . The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical research ers in Melbourne , Australia . Patients with obesity hypoventilation syndrome , previous bariatric surgery , contraindications to bariatric surgery , or significant cardiopulmonary , neurological , vascular , gastrointestinal , or neoplastic disease were excluded . INTERVENTIONS Patients were r and omized to a conventional weight loss program that included regular consultations with a dietitian and physician , and the use of very low-calorie diets as necessary ( n = 30 ) or to bariatric surgery ( laparoscopic adjustable gastric b and ing ; n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to r and omization . Secondary outcomes were changes in weight , CPAP adherence , and functional status . RESULTS Patients lost a mean of 5.1 kg ( 95 % CI , 0.8 to 9.3 kg ) in the conventional weight loss program compared with 27.8 kg ( 95 % CI , 20.9 to 34.7 kg ) in the bariatric surgery group ( P < .001 ) . The AHI decreased by 14.0 events/hour ( 95 % CI , 3.3 to 24.6 events/hour ) in the conventional weight loss group and by 25.5 events/hour ( 95 % CI , 14.2 to 36.7 events/hour ) in the bariatric surgery group . The between-group difference was -11.5 events/hour ( 95 % CI , -28.3 to 5.3 events/hour ; P = .18 ) . CPAP adherence did not differ between the groups . The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score ( mean , 9.3 [ 95 % CI , 0.5 to 18.0 ] ; P = .04 ) . CONCLUSION Among a group of obese patients with OSA , the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss . TRIAL REGISTRATION anzctr.org Identifier : 12605000161628 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 Objective Our objective was to investigate the role of bile acids in  hepatic steatosis reduction after vertical sleeve gastrectomy ( VSG ) . Design and Methods  High fat diet ( HFD ) induced obese C57Bl/6 mice were r and omized to : VSG , Sham operation ( Sham ) , Sham operation with pair feeding to VSG ( Sham-PF ) , or non-surgical controls ( Naïve ) . All mice were on HFD until sacrifice . Mice were observed post-surgery and data for body weight , body composition , metabolic parameters , serum bile acid level and composition were collected . Further hepatic gene expression by RNAseq and RT-PCR analysis was assessed . Results VSG and Sham-PF mice lost equal weight post-surgery while VSG mice had the lowest hepatic triglyceride content at sacrifice . The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss . Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid . These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes . Conclusion VSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone . VSG surgery increases serum bile acids that correlate with weight lost post-surgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis The physiological role of glucagon-like peptide-1 7 - 36 amide ( GLP-1 7 - 36 ) in man was investigated . GLP-1 7 - 36-like immunoreactivity was found in the human bowel ; its circulating level rose after oral glucose and after a test breakfast . When it was infused into seven volunteers at a rate to mimic its postpr and ial plasma concentration in the fasting state , plasma insulin levels rose significantly and glucose and glucagon concentrations fell . During an intravenous glucose load , it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations , compared with a control saline infusion , even inducing postinfusion reactive hypoglycaemia . By comparison , infusion of glucose-dependent insulinotropic peptide ( GIP ) to physiological levels was less effective in stimulating insulin release . These observations suggest that GLP-1 7 - 36 is a physiological incretin and that it is more powerful than GIP . The observation of greatly increased postpr and ial plasma GLP-1 7 - 36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder 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 Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome . Changes in intestinal and hepatic physiology after ileal interposition ( transposition ) surgery ( IIS )  are not well understood . Our aim was to eluci date the adaptation of the interposed ileum , which we hypothesized , would lead to early bile acid reabsorption in the interposed ileum , thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments . Rats with diet-induced obesity were r and omized to IIS  , with 10 cm of ileum repositioned distal to the duodenum , or sham surgery . A subgroup of sham rats was pair-fed to IIS rats . Physiological parameters were measured until 6 wk postsurgery . IIS rats ate less and lost more weight for the first 2 wk postsurgery . At study completion , body weights were not different , but IIS rats had reversed components of the metabolic syndrome . The interposed ileal segment adapted to a more jejunum-like villi length , mucosal surface area , and GATA4/ILBP mRNA . The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi . IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum , suggesting an early and efficient reabsorption of primary bile acids . IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss . There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR , SHP , or NTCP expression . IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling . There is early reabsorption of primary bile acids despite selective " jejunization " of the interposed ileal segment . Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery 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  
    Output:
    