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Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.

ABSTRACT: Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45-55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672).

SUBMITTER: Biemann R

PROVIDER: S-EPMC4958948 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.

Biemann Ronald R Penner Marina M Borucki Katrin K Westphal Sabine S Luley Claus C Rönicke Raik R Biemann Kathleen K Weikert Cornelia C Lux Anke A Goncharenko Nikolai N Marschall Hanns-Ulrich HU Schneider Jochen G JG Isermann Berend B

Scientific reports 20160725

Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45-55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via tel ...[more]

PMID: 27452603

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Project description:BackgroundRecent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain.MethodsIn a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance.ResultsSoluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml(-1) (-3.0 (95% confidence interval (CI)=-0.5 to -5.5)), P<0.001 and free leptin index decrease was 43% smaller; -62±15 vs -109±20 (-47 (95% CI=-11 to -83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (-2.3 kg (95% CI=-0.6 to -4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=-0.6 to -1)), P<0.001. Fasting glucose was decreased by an additional -0.2±0.1 mmol l(-1) in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l(-1) to the level before weight loss (-0.5mmol l(-1) (95% CI=-0.1 to -0.9)), P<0.005. Meal response of peptide PYY3-36 was higher at week 52 in the GLP-1RA group compared with the control group, P<0.05.ConclusionsThe weight maintaining effect of GLP-1RAs may be mediated by smaller decrease in free leptin and higher PYY3-36 response. Low dose GLP-1RA therapy maintained 12% weight loss for 1 year and may prevent pre-diabetes in obesity.

Project description:BackgroundBile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro.MethodsThirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group). Body weights and blood lipid profiles were measured in all groups after 16 weeks of treatment. The concentrations of bile acids in bile and faeces were analysed using HPLC-MS (high-performance liquid chromatography-mass spectrometry). Gene transcription and the expression levels associated with bile acid absorption in the small intestines were determined using real-time PCR and Western blot. Ileal bile acid binding protein (I-BABP) was analysed using immunofluorescence. The effects of MCFAs on the permeability of bile acid (cholic acid, CA) in Caco-2 cell monolayers and I-BABP expression levels in Caco-2 cells treated with caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0) and oleic acid (C18:1) were determined.ResultsMice in the CR-MCT group exhibited lower body weights and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a higher HDL-C/LDL-C ratio than the CR-LCT group (P < 0.05). The concentrations of primary bile acids (primarily CA) and secondary bile acids in faeces and secondary bile acids in bile in the CR-MCT group were significantly higher than in the CR-LCT group (P < 0.05). C8:0 and C10:0 decreased the permeability of CA in Caco-2 cell monolayers. MCT/MCFAs (C8:0 and C10:0) inhibited I-BABP gene expression in the small intestines and Caco-2 cells (P < 0.05).ConclusionsMCT slowed the body weight increase and promoted the excretion of bile acids. MCT lowered serum cholesterol levels at least partially via reduction of bile acid absorption in the small intestine by inhibition of I-BABP expression. Our results provide the basis for clinical trials of MCT as a dietary supplement for lowering plasma cholesterol and reducing risk of CHD.

Project description:ImportanceBile acids play essential roles in metabolic modulation. Excessive serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes; however, their association with the risk of intrauterine growth restriction (IUGR) remains unclear.ObjectiveTo investigate the association between maternal sTBA concentration during pregnancy and the risk of IUGR.Design, setting, and participantsThis retrospective cohort study included pregnant individuals who delivered live singleton neonates and had regular antenatal examination records available at a hospital-based center in Shanghai, China, from 2014 to 2018. Data were analyzed from July to November 2020.ExposuresMaternal sTBA concentration during pregnancy.Main outcomes and measuresFetal birth weight and probability of low birth weight (LBW) and IUGR.ResultsThis study included 68 245 singleton pregnancies with live births for analysis. The mean (SD) age of the pregnant individuals was 30.5 (3.8) years, 67 168 patients (98.4%) were Han, and 50 155 (73.5%) were nulliparous. Nonlinear regression models suggested that there was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight, with a steep decrease in birth weight at high sTBA levels (estimated mean [SE] birth weight for sTBA of 40.8 ug/mL, 2879 [39.9] g) and greater birth weights at lower sTBA levels (estimated mean [SE] birth weight for sTBA 0.4 μg/mL, 3290 [3.9] g; and for 4.1 μg/mL, 3334 [1.6] g). Lower birth weight and a higher incidence of IUGR were observed in patients with gestational hypercholanemia (sTBA ≥4.08 μg/mL) compared with those without gestational hypercholanemia (birth weight: estimated adjusted mean [SE], 3309 [3.32] vs 3338 [0.80] g; P = .005; incidence of IUGR: 62 of 4467 [1.4%] vs 312 of 63 778 [0.5%]; P < .001). Moreover, compared with patients with sTBA concentrations of less than 4.08 μg/mL, those with gestational hypercholanemia had an increased risk of LBW (adjusted odds ratio [aOR], 1.29; 95% CI, 1.09-1.53) and IUGR (aOR, 2.18; 95% CI, 1.62-2.91). In addition, there was an additive interaction between hypertensive disorders in pregnancy (HDP) and hypercholanemia on LBW and IUGR risk. The highest risks of LBW and IUGR were found in pregnant individuals with both HDP and hypercholanemia compared with those with normotensive pregnancies with sTBA concentrations less than 4.08 μg/mL (LBW: aOR, 9.13; 95% CI, 6.88-12.12; IUGR: aOR, 19.14; 95% CI, 12.09-30.28).Conclusions and relevanceThis study found that gestational hypercholanemia was associated with an increased risk of LBW and IUGR, especially in pregnant individuals with HDP. Therefore, it would be meaningful to monitor sTBA concentration during the follow-up of pregnancies with potential IUGR.

Project description:Host-gut microbiota metabolic interactions are closely associated with health and disease. A manifestation of such co-metabolism is the vast structural diversity of bile acids (BAs) involving both oxidative stereochemistry and conjugation. Herein, we describe the development and validation of a LC-MS-based method for the analysis of human C24 BA metabolome in serum and urine. The method has high throughput covering the discrimination of oxidative stereochemistry of unconjugated species in a 15-min analytical cycle. The validated quantitative performance provided an indirect way to ascertain the conjugation patterns of BAs via enzyme-digestion protocols that incorporated the enzymes, sulfatase, β-glucuronidase, and choloylglycine hydrolase. Application of the method has led to the detection of at least 70 unconjugated BAs including 27 known species and 43 newly found species in the post-prandial serum and urine samples from 7 nonalcoholic steatohepatitis patients and 13 healthy volunteers. Newly identified unconjugated BAs included 3α, 12β-dihydroxy-5β-cholan-24-oic acid, 12α-hydroxy-3-oxo-5β-cholan-24-oic acid, and 3α, 7α, 12β-trihydroxy-5β-cholan-24-oic acid. High-definition negative fragment spectra of the other major unknown species were acquired to facilitate future identification endeavors. An extensive conjugation pattern is the major reason for the "invisibility" of the newly found BAs to other common analytical methods. Metabolomic analysis of the total unconjugated BA profile in combination with analysis of their conjugation patterns and urinary excretion tendencies have provided substantial insights into the interconnected roles of host and gut microbiota in maintaining BA homeostasis. It was proposed that the urinary total BA profile may serve as an ideal footprint for the functional status of the host-gut microbial BA co-metabolism. In summary, this work provided a powerful tool for human C24 BA metabolome analysis that bridges the gap between GC-MS techniques in the past age and LC-MS techniques currently prevailing in biomedical researches. Further applications of the present method in clinical, translational research, and other biomedical explorations will continue to boost the construction of a host-gut microbial co-metabolism network of BAs and thus facilitate the decryption of BA-mediated host-gut microbiota crosstalk in health and diseases. Graphical abstract ᅟ.

Dataset Information

Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.

Publications

Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.

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