Targeting bile acid metabolism in obesity reduction: A systematic review and meta‐analysis

So, Sik Yu; Yeung, Chris Ho Ching; Schooling, CM; El‐Nezami, Hani

doi:10.1111/obr.13017

Cited by 23 publications

(15 citation statements)

References 105 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is a well observed fact that bariatric procedures significantly reduce levels of cholesterol and LDL cholesterol ( 24 ). Among the hypothesized mechanisms contributing to reduced cholesterol levels after bariatric surgery are a decreased intestinal cholesterol absorption, an increased trans-intestinal cholesterol excretion as well as an increased flux of cholesterol into bile acid synthesis due to augmented fecal excretion of bile acids ( 25 , 26 ). Interestingly, there are studies suggesting a direct role of DPP4 in the regulation of cholesterol levels.…”

Section: Discussionmentioning

confidence: 99%

Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

et al. 2021

View full text Add to dashboard Cite

Purpose Dipeptidyl peptidase 4 (DPP4) is expressed and secreted by adipocytes. DPP4 induces insulin resistance independently of its effect on glucagon-like peptide 1, thus it is conceivable that DPP4 directly contributes to metabolic dysfunction in patients with morbid obesity. The aim of this study was to investigate the impact of weight loss induced by bariatric surgery on DPP4 activity, and whether these changes are associated with improvements in markers of metabolic dysfunction and fatty liver disease. Materials and Methods We included 68 non-diabetic patients who underwent bariatric surgery. Serum DPP4 activity was measured using a fluorogenic substrate before and after surgery. Results Results: After a median follow-up period of 12 (IQR 11-17) months, median serum DPP4 activity decreased from 230 (IQR: 194-273) to 193 (164-252) pmol/min (p=0.012). The decrease in DPP4 activity was significantly correlated with decreases in BMI, improved cholesterol levels, reduced hepatic injury markers as well as improved post-prandial insulin sensitivity. After multivariable adjustment, ΔDPP4 activity remained significantly associated with Δcholesterol (beta=0.341, p=0.025), ΔLDL cholesterol (beta=0.350, p=0.019), Δgamma-glutamyltransferase (beta=0.323, p=0.040) and ΔMatsuda index (beta=-0.386, p=0.045). Conclusion We demonstrated that weight loss induced by bariatric surgery results in decreased circulating DPP4 activity beyond the initial phase of weight loss. The associations between decreased DPP4 activity and improved cholesterol levels as well as hepatic injury markers point towards pleiotropic effects of DPP4 beyond glucose metabolism which warrant further investigation.

show abstract

Section: Discussionmentioning

confidence: 99%

Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Previous studies have also shown a link between increasing BMI and primary BAD although – unlike ours – have not performed direct comparisons of BAD prevalence rates in patients with chronic diarrhoea stratified according to the World Health Organisation weight classification system [ 20 , 21 , 33 ]. The link between increasing BMI and primary BAD is intriguing, with a recent systematic review and meta-analysis confirming altered bile acid metabolism in obesity [ 34 ]. This is evidenced by individuals with obesity having lower serum FGF19, elevated serum bile acid precursors, increased bile acid synthesis and luminal excretion, with shorter colonic transit times [ 3 , 21 , [33] , [34] , [35] ].…”

Section: Discussionmentioning

confidence: 99%

“…The link between increasing BMI and primary BAD is intriguing, with a recent systematic review and meta-analysis confirming altered bile acid metabolism in obesity [ 34 ]. This is evidenced by individuals with obesity having lower serum FGF19, elevated serum bile acid precursors, increased bile acid synthesis and luminal excretion, with shorter colonic transit times [ 3 , 21 , [33] , [34] , [35] ]. The pathophysiological basis for this association is unclear, although some plausible explanations have been provided.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria

et al. 2020

View full text Add to dashboard Cite

Background A high prevalence of primary bile acid diarrhoea (BAD) has been reported for Rome III defined irritable bowel syndrome (IBS)-diarrhoea and functional diarrhoea. We determined whether this still applies under the contemporaneous Rome IV criteria, given that the latter characterises IBS-diarrhoea as having more frequent abdominal pain compared with previous iterations, whilst no longer recognising abdominal discomfort. Methods Patients referred for a 75 SeHCAT test completed a baseline questionnaire comprising, i) demographic data, ii) risk factors for BAD (inflammatory bowel disease, bowel resection, cholecystectomy, microscopic colitis, celiac disease, abdominal-pelvic radiotherapy), iii) the Rome III and IV bowel disorder questionnaire, and iv) mood and somatisation scores. A diagnosis of BAD constituted a 75 SeHCAT of ≤15%, with moderate to severe disease being defined as ≤10% and ≤5%, respectively. Findings Of 300 patients with complete dataset, 184 had no risk factors for BAD and fulfilled criteria for either IBS-diarrhoea or functional diarrhoea. The prevalence of primary BAD was 38% ( n = 70/184), with almost half having moderate ( n = 16) to severe ( n = 17) disease. Using the Rome III criteria, the prevalence of primary BAD was 36% in IBS-diarrhoea ( n = 63/173) and 64% ( n = 7/11) in functional diarrhoea; p = 0.11. Using the Rome IV criteria, the prevalence of primary BAD was 38% ( n = 53/139) in IBS-diarrhoea and 38% ( n = 17/45) in functional diarrhoea; p = 0.97. Patients with primary BAD experienced more frequent loose stools ( p = 0.01) and had a higher body mass index ( p <0.0001) compared to those without BAD, but otherwise no significant differences were seen in age, gender, mood, somatisation, or abdominal pain. The presence of primary BAD in patients classified as overweight or obese was approximately 40% and 60%, respectively. Interpretation Over a third of patients with Rome IV IBS-diarrhoea or functional diarrhoea have primary BAD, similar to Rome III. We therefore recommend that, in secondary care settings, generic testing for primary BAD should be considered in patients presenting with chronic diarrhoea of presumed functional origin regardless of concomitant abdominal pain. Centres that lack tests for primary BAD, and who empirically treat instead, may consider targeting patients who are overweight or obese.

show abstract

“…Several studies indicate that bariatric surgery leads to an increase in plasma levels of bile acids (BA) [51][52][53][54][55][56]. After RYGB, an increase was found in fasting and postprandial BA, with parallel alterations in composition.…”

Section: Bile Acidsmentioning

confidence: 99%

Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation

2021

View full text Add to dashboard Cite

Bariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB—less after SG—bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.

show abstract

Targeting bile acid metabolism in obesity reduction: A systematic review and meta‐analysis

Cited by 23 publications

References 105 publications

Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

Decrease of dipeptidyl peptidase 4 activity is associated with weight loss after bariatric surgery

High prevalence of primary bile acid diarrhoea in patients with functional diarrhoea and irritable bowel syndrome-diarrhoea, based on Rome III and Rome IV criteria

Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation

Contact Info

Product

Resources

About