Effects of Bariatric Surgery on Serum Bile Acid Composition and Conjugation in a Diabetic Rat Model

Wu, Qunzheng; Zhang, Xiang; Zhong, Maiying; Han, Huijian; Liu, Shaozhuang; Li, Teng; Wang, Meng; Guo, Wei; Xie, Haibin; Hu, Sanyuan; Zhang, Guangyong

doi:10.1007/s11695-016-2087-2

Cited by 28 publications

(29 citation statements)

References 45 publications

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“…Furthermore, coprophagy causes recirculation of secondary BAs, which increases their systemic concentrations (Groen, Kunne, & Oude Elferink, ; Krief, Jamart, & Hladik, ) in minipig and chimpanzee. This is in agreement with previous reports, where lowest primary/secondary BA ratios were observed in rabbit (1.1‐fold; Kasbo et al, ) and pig (1.2‐fold;Spinelli et al, ; Tsai et al, ), while it was highest in mice (2.6–8.6‐fold; Chen et al, ; Han et al, ), rat (2.1–7‐fold; Aoki et al, ; Wu et al, ) and hamster (5.4‐fold; Kasbo et al, ).…”

Section: Discussionsupporting

confidence: 92%

“…We observed major species differences in multiple aspects of the plasma BA profiles. Similar to previous data our results showed that the highest total concentrations of plasma BAs were observed in the rat and pig (Garcia‐Canaveras, et al, ; Gunness et al, ; Tsai, Zhong, Weng, Huang, & Hsieh, ; Wu et al, ) and that G‐amidation was predominant in human and pig (Han et al, ; Spinelli et al, ; Tsai et al, ), while T‐amidation was predominant in rat, mice and dog (Ando et al, ; Aoki et al, ; Chen et al, ; Han et al, ; Marschall et al, ; Washizu, Ishida, Washizu, Tomoda, & Kaneko, ; Washizu, Tomoda, & Kaneko, ; Wu et al, ). Furthermore, in line with previous data we found that the BA pool in plasma was primarily composed of di‐OH BAs in humans, while tri‐OH BAs were the main components in rat, mice and hamster (Table ).…”

Section: Discussionsupporting

confidence: 90%

“…In contrast, CA/CDCA ratio was low (0.3–0.6) in human (Brufau et al, ; Ferslew et al, ; Han et al, ; Roberts et al, ; Trottier et al, ; Washizu et al, ; Wewalka, Patti, Barbato, Houten, & Goldfine, ; Xie et al, ) and 0.024 in pig (Spinelli et al, ; Tsai et al, ). Similarly, the 12α‐OH/non‐12α‐OH BA ratio was 0.7, 0.4 and 0.004 in human (Brufau et al, ; Ferslew et al, ; Han et al, ; Roberts et al, ; Trottier et al, ; Wewalka et al, ; Xie et al, ), pig (Spinelli et al, ; Tsai et al, ) and rat (Ando et al, ; Aoki et al, ; Spinelli et al, ; Wu et al, ), respectively.…”

Section: Discussionmentioning

confidence: 95%

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Species differences in bile acids I. Plasma and urine bile acid composition

Thakare

Alamoudi

Gautam

et al. 2018

J of Applied Toxicology

103

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Maintenance of bile acid (BA) homeostasis is essential to achieve their physiologic functions and avoid their toxic effects. The marked differences in BA composition between preclinical safety models and humans may play a major role in the poor prediction of drug-induced liver injury using preclinical models. We compared the composition of plasma and urinary BAs and their metabolites between humans and several animal species. Total BA pools and their composition varied widely among different species. Highest sulfation of BAs was observed in human and chimpanzee. Glycine amidation was predominant in human, minipig, hamster and rabbit, while taurine amidation was predominant in mice, rat and dogs. BA profiles consisted primarily of tri-OH BAs in hamster, rat, dog and mice, di-OH BAs in human, rabbit and minipig, and mono-OH BA in chimpanzee. BA profiles comprised primarily hydrophilic and less toxic BAs in mice, rat, pig and hamster, while it primarily comprised hydrophobic and more toxic BAs in human, rabbit and chimpanzee. Therefore, the hydrophobicity index was lowest in minipig and mice, while it was highest in rabbit, monkey and human. Glucuronidation and glutathione conjugation were low in all species across all BAs. Total concentration of BAs in urine was up to 10× higher and more hydrophilic than plasma in most species. This was due to the presence of more tri-OH, amidated, sulfated and primary BAs, in urine compared to plasma. In general, BA profiles of chimpanzee and monkeys were most similar to human, while minipig, rat and mice were most dissimilar to human.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Species differences in bile acids I. Plasma and urine bile acid composition

Thakare

Alamoudi

Gautam

et al. 2018

J of Applied Toxicology

103

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“…For example, the duodenal-jejunal bypass isolates the ‘bypass’ portion of RYGB in the absence of gastric restriction and has metabolic effects in obese and lean rodents (Habegger et al, 2014; Kindel et al, 2011; 2009; B. Li et al, 2013; Rubino and Marescaux, 2004; Wu et al, 2016; X. Zhang et al, 2015).…”

Section: Bile Acids and Obesitymentioning

confidence: 99%

Bile acids and bariatric surgery

Albaugh

Banan

Ajouz

et al. 2017

Molecular Aspects of Medicine

111

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Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40-80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short-and long-term metabolic improvements after bariatric surgery is critically examined.

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“…For example, Wu et al . performed duodenal-jejunal bypass (DJB) and sleeve gastrectomy in diabetic rats and found that the expression of amino acid N-acyltransferase Baat was up-regulated with increased serum conjugated bile acid levels 28 . As such, further investigation is warranted to understand the dynamics of Baat expression following RYGB and how that impacts the levels of conjugated bile acids either after fasting or post-prandial states.…”

Section: Discussionmentioning

confidence: 99%

Multi-omic network-based interrogation of rat liver metabolism following gastric bypass surgery featuring SWATH proteomics

et al. 2017

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Morbidly obese patients often elect for Roux-en-Y gastric bypass (RYGB), a form of bariatric surgery that triggers a remarkable 30% reduction in excess body weight and reversal of insulin resistance for those who are type II diabetic. A more complete understanding of the underlying molecular mechanisms that drive the complex metabolic reprogramming post-RYGB could lead to innovative non-invasive therapeutics that mimic the beneficial effects of the surgery, namely weight loss, achievement of glycemic control, or reversal of non-alcoholic steatohepatitis (NASH). To facilitate these discoveries, we hereby demonstrate the first multi-omic interrogation of a rodent RYGB model to reveal tissue-specific pathway modules implicated in the control of body weight regulation and energy homeostasis. In this study, we focus on and evaluate liver metabolism three months following RYGB in rats using both SWATH proteomics, a burgeoning label free approach using high resolution mass spectrometry to quantify protein levels in biological samples, as well as MRM metabolomics. The SWATH analysis enabled the quantification of 1378 proteins in liver tissue extracts, of which we report the significant down-regulation of Thrsp and Acot13 in RYGB as putative targets of lipid metabolism for weight loss. Furthermore, we develop a computational graph-based metabolic network module detection algorithm for the discovery of non-canonical pathways, or sub-networks, enriched with significantly elevated or depleted metabolites and proteins in RYGB-treated rat livers. The analysis revealed a network connection between the depleted protein Baat and the depleted metabolite taurine, corroborating the clinical observation that taurine-conjugated bile acid levels are perturbed post-RYGB.

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Effects of Bariatric Surgery on Serum Bile Acid Composition and Conjugation in a Diabetic Rat Model

Abstract: The preferentially elevated serum taurine-conjugated BAs were similar after different bariatric surgeries, and the enhanced conjugation of BAs in the liver might account for the changed serum BAs profiles.

Cited by 28 publications

References 45 publications

Species differences in bile acids I. Plasma and urine bile acid composition

Species differences in bile acids I. Plasma and urine bile acid composition

Bile acids and bariatric surgery

Multi-omic network-based interrogation of rat liver metabolism following gastric bypass surgery featuring SWATH proteomics

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