Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss

Seyfried, Florian; Phetcharaburanin, Jutarop; Glymenaki, Maria; Nordbeck, Arno; Hankir, Mohammed K.; Nicholson, Jeremy K.; Holmes, Elaine; Marchesi, Julian R.; Li, Jia V.

doi:10.1080/19490976.2021.1875108

Cited by 20 publications

(29 citation statements)

References 65 publications

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“…However, it is possible that the changes in plasma metabolites present after RYGB and BWM, but not after PYY3-36 + liraglutide, are responsible for the detected changes in hypothalamic gene expression. This is supported by the profound changes we previously found in plasma metabolites in RYGB and BWM compared with Sham Zucker Fatty rats [ 63 ].…”

Section: Discussionsupporting

confidence: 80%

Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats

et al. 2021

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Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing. Results: While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK–STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.

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Section: Discussionsupporting

confidence: 80%

Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats

et al. 2021

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“…BCAA catabolic intermediates were more weakly correlated with each other. Aromatic amino acids were more strongly correlated with BCAAs than they were with host-microbial co-metabolites, despite the fact that altered host-microbial aromatic amino acid metabolism resulting in the production of metabolites such as N-phenylacetylglycine and 4-hydroxyphenylacetate has been consistently reported following RYGB [28][29][30][31][32][33].…”

Section: Inter-peak Correlations and Abundance By Study Arm And Timep...mentioning

confidence: 95%

Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

et al. 2022

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In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2-year follow-up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary 1H-NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6-month follow-up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host–microbial co-metabolites (N-phenylacetylglycine, trimethylamine N-oxide, and 4-aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched-chain amino acids (BCAAs) and related catabolites (valine, leucine, 3-hydroxyisobutyrate, 3-hydroxyisovalerate, and 3-methyl-2-oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM.

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“…For example, the biosynthesis of a microbially-derived neuroactive intermediate, GABA (γ-amino butyric acid), is enhanced after RYGB, particularly due to the post-surgical abundance of Enterococcus spp. [ 191 , 192 ]. GABA has been reported to regulate gut motility and may affect food transition to the gut.…”

Section: Effects Of Bariatric Surgery On the Gut Microbiotamentioning

confidence: 99%

“…Bariatric surgery, and especially RYGB, plays also an important role in bile acid (BAs) metabolism [ 197 ]. BAs have been shown to regulate glucose metabolism by increasing insulin sensitivity and reducing gluconeogenesis [ 130 ]; in particular, taurine-conjugated BAs promote GLP-1 secretion and energy balance by activating TGR5 [ 191 ]. In addition, BAs regulate the composition of microbial communities and the final outcome of surgical obesity in terms of body weight [ 158 ].…”

Section: Effects Of Bariatric Surgery On the Gut Microbiotamentioning

confidence: 99%

“…However, Seyfried et al [ 191 ] conducted a study on the effects of RYGB on BAs levels in portal vein and peripheral plasma, demonstrating that caloric restriction had a more profound impact on the BA pools than RYGB. In fact, 3α-hydroxy-12 ketolithocholic acid, taurocheno-deoxycholic acid and tauro-β muricholic acid, were found to be higher in the portal vein blood compared to peripheral circulation in both RYGB and Sham-non-obese, but not in the Sham-obese group.…”

Section: Effects Of Bariatric Surgery On the Gut Microbiotamentioning

confidence: 99%

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Bariatric Surgery and Liver Disease: General Considerations and Role of the Gut–Liver Axis

et al. 2021

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Weight loss is a therapeutic solution for many metabolic disorders, such as obesity and its complications. Bariatric surgery aims to achieve lasting weight loss in all patients who have failed after multiple dietary attempts. Among its many benefits, it has been associated with the regression of non-alcoholic fatty liver disease (NAFLD), which is often associated with obesity, with evidence of substantial improvement in tissue inflammation and fibrosis. These benefits are mediated not only by weight loss, but also by favorable changes in systemic inflammation and in the composition of the gut microbiota. Changes in microbial metabolites such as short-chain fatty acids (SCFAs), capable of acting as endocrine mediators, and bile acids (BAs) as well as modifications of the gut-brain axis, are among the involved mechanisms. However, not all bariatric surgeries show beneficial effects on the liver; those leading to malabsorption can cause liver failure or a marked worsening of fibrosis and the development of cirrhosis. Nevertheless, there are still many unclear aspects, including the extent of the benefits and the magnitude of the risks of bariatric surgery in cirrhotic patients. In addition, the usefulness and the safety of these procedures in patients who are candidates to or who have undergone liver transplant need solid supporting evidence. This paper aims to review literature data on the use of bariatric surgery in the setting of chronic liver disease.

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Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss

Abstract: Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss,

Cited by 20 publications

References 65 publications

Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats

Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats

Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

Bariatric Surgery and Liver Disease: General Considerations and Role of the Gut–Liver Axis

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