scholarly journals Bile Acid Signaling: Mechanism for Bariatric Surgery, Cure for NASH?

2015 ◽  
Vol 33 (3) ◽  
pp. 440-446 ◽  
Author(s):  
Rohit Kohli ◽  
Andriy Myronovych ◽  
Brandon K. Tan ◽  
Rosa-Maria Salazar-Gonzalez ◽  
Lili Miles ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Adjustable Gastric Band ◽  
Metabolic Effects ◽  
Signaling Mechanism ◽  
Serum Bile Acids ◽  
Long Run

Bariatric surgery is the most effective and durable treatment option for obesity today. More importantly, beyond weight loss, bariatric procedures have many advantageous metabolic effects including reversal of obesity-related liver disease - nonalcoholic steatohepatitis (NASH). NASH is an important comorbidity of obesity given that it is a precursor to the development of liver cirrhosis that may necessitate liver transplantation in the long run. Simultaneously, we and others have observed increased serum bile acids in humans and animals that undergo bariatric surgery. Specifically, our preclinical studies have included experimental procedures such as ‘ileal transposition' or bile diversion and established procedures such as Roux-en-Y gastric bypass and the adjustable gastric band. Importantly, these effects are not simply the result of weight loss since our data show that the resolution of NASH and increase in serum bile acids are not seen in rodents that lose an equivalent amount of weight via food restriction. In particular, we have studied the role of altered bile acid signaling, in the potent impact of a bariatric procedure termed ‘vertical sleeve gastrectomy' (VSG). In this review we focus on the mechanisms of NASH resolution and weight loss after VSG surgery. We highlight the fact that bariatric surgeries can be used as ‘laboratories' to dissect the mechanisms by which these procedures work to improve obesity and fatty liver disease. We describe key bile acid signaling elements that may provide potential therapeutic targets for ‘bariatric-mimetic technologies' that could produce benefits similar to bariatric surgery - but without the surgery!

scholarly journals Impact of Fibroblast Growth Factors 19 and 21 in Bariatric Metabolism

2017 ◽  
Vol 35 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Ashley Patton ◽  
Farooq H. Khan ◽  
Rohit Kohli
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Bile Acid ◽  
Health Condition ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Fibroblast Growth ◽  
Long Term Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Distal Small Intestine

Background: Bariatric surgery is a popular and effective therapeutic intervention for obesity, which is an abnormal health condition that is prevalent worldwide. Metabolic improvements that precede weight loss after bariatric surgery may be mediated, in part, through the fibroblast growth factor (FGF) 15/19 and FGF21 signaling pathways. Both FGF15/19 and FGF21 are hormone-like members of the FGF family and exert their metabolic effects in an endocrine manner. Enhanced bile acid recycling after bariatric surgery leads to increased circulating levels of FGF15/19 in the distal small intestine. Synthesis of FGF21 is upregulated predominately in the fasting state through peroxisome proliferator-activated receptor pathways and to a lesser extent by FGF15/19. Key Messages: The biological functions of FGF15/19 and FGF21 are diverse and complicated. The tissue targeted effects of FGF15/19 and FGF21 of importance after bariatric surgery include the regulation of hepatic bile acid biosynthesis and ketogenesis as well as thermogenesis in adipose tissue, respectively. Furthermore, FGF15/19 and FGF21 function to regulate carbohydrate and lipid metabolism. Conclusion: The long-term effects of bariatric surgery on weight loss are undisputable. However, the mechanism for improvements in glucose and lipid homeostasis observed shortly after bariatric surgery is less understood. This review article attempts to describe the known metabolic effects of FGF15/19 and FGF21 that may potentiate these improvements after bariatric surgery.

Serum Bile Acids in Patients with Liver Disease

1965 ◽  
Vol 11 (5) ◽  
pp. 547-553 ◽  
Author(s):  
Samuel J Levin ◽  
Morton K Schwartz
Keyword(s):  
Alkaline Phosphatase ◽  
Liver Disease ◽  
Bile Acid ◽  
Liver Metastases ◽  
Viral Hepatitis ◽  
Bile Acids ◽  
Liver Diseases ◽  
Serum Bile Acids ◽  
Yield Information

Abstract By means of a sensitive fluorometric technic, serum bile acids were determined in patients with various liver diseases. Correlations were shown between the bile acid values and those of transaminase and alkaline phosphatase in cases of liver metastases, and bile acid and transaminase values in cases of viral hepatitis. For most clinical purposes, however, the determination does not yield information which cannot be obtained more readily using currently accepted methods.

scholarly journals Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries

2018 ◽  
Vol 314 (5) ◽  
pp. G537-G546 ◽  
Author(s):  
Meng Wei ◽  
Yi Shao ◽  
Qiao-ran Liu ◽  
Qun-zheng Wu ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Bile Acids ◽  
Rat Model ◽  
Enterohepatic Circulation ◽  
Metabolic Effects ◽  
Diabetic Rat ◽  
Jejunal Bypass ◽  
Diabetic Rat Model

Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.

scholarly journals Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1496
Author(s):  
Noemí Cabré ◽  
Yi Duan ◽  
Cristina Llorente ◽  
Mary Conrad ◽  
Patrick Stern ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Liver Steatosis ◽  
Elevated Serum ◽  
Bile Acid Metabolism ◽  
Functional Changes ◽  
Serum Bile Acids ◽  
Gnotobiotic Mice ◽  
Related Liver Disease

Alcohol-related liver disease is associated with intestinal dysbiosis. Functional changes in the microbiota affect bile acid metabolism and result in elevated serum bile acids in patients with alcohol-related liver disease. The aim of this study was to identify the potential role of the bile acid sequestrant colesevelam in a humanized mouse model of ethanol-induced liver disease. We colonized germ-free (GF) C57BL/6 mice with feces from patients with alcoholic hepatitis and subjected humanized mice to the chronic–binge ethanol feeding model. Ethanol-fed gnotobiotic mice treated with colesevelam showed reduced hepatic levels of triglycerides and cholesterol, but liver injury and inflammation were not decreased as compared with non-treated mice. Colesevelam reduced hepatic cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1) protein expression, although serum bile acids were not lowered. In conclusion, our findings indicate that colesevelam treatment mitigates ethanol-induced liver steatosis in mice.

scholarly journals Serum Bile Acids in Cholestatic Liver Disease: Their Measurement and Significance

1972 ◽  
Vol 9 (1-6) ◽  
pp. 67-73 ◽  
Author(s):  
G. M. Murphy
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Specific Method ◽  
Cholestatic Liver Disease ◽  
Serum Bile Acids

A relatively rapid and specific method for the estimation of serum individual bile acids, conjugated and free, in small volumes (1 ml) of sera from patients with liver disease has been developed. This method has been applied to a study of 25 patients with liver disease. Cholestatic liver disease has been found to be associated with an increase in serum monohydroxy bile acids which appear to be of an unsaturated nature. No association was found between the concentration of any particular bile acid and the presence or absence of pruritus.

scholarly journals Utility of Fibroscan XL to assess the severity of non-alcoholic fatty liver disease in patients undergoing bariatric surgery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew Yang ◽  
Melinda Nguyen ◽  
Irene Ju ◽  
Anthony Brancatisano ◽  
Brendan Ryan ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Stiffness ◽  
Convincing Evidence ◽  
Alcoholic Fatty Liver ◽  
Post Surgery

AbstractSignificant weight loss can modify the progression of Nonalcoholic fatty liver disease (NAFLD) with the most convincing evidence coming from bariatric surgery cohorts. Effective ways to non-invasively characterise NAFLD in these patients has been lacking, with high Fibroscan failure rates reported. We prospectively evaluated the utility of Fibroscan using XL-probe over a two-year period. 190 consecutive patients undergoing bariatric surgery were followed as part of their routine care. All patients had Fibroscan performed on the day of surgery and at follow-up a mean of 13 months (± 6.3) later. The majority of patients were female (82%) with mean age of 42. Fibroscan was successful in 167 (88%) at baseline and 100% at follow up. Patients with a failed Fibroscan had higher body mass index (BMI) and alanine transaminase (ALT), but no difference in FIB-4/NAFLD score. Mean baseline Liver stiffness measurement was 5.1 kPa, with 87% of patients classified as no fibrosis and 4% as advanced fibrosis. Mean baseline controlled attenuation parameter was 291, with 78% having significant steatosis, 56% of which was moderate-severe. Significant fibrosis was associated with higher BMI and HbA1c. Significant steatosis was associated with higher BMI, ALT, triglycerides and insulin resistance. Mean follow up time was 12 months with weight loss of 25.7% and BMI reduction of 10.4 kg/m2. Seventy patients had repeat fibroscan with reductions in steatosis seen in 90% and fibrosis in 67%. Sixty-four percent had complete resolution of steatosis. Fibroscan can be performed reliably in bariatric cohorts and is useful at baseline and follow-up. Significant steatosis, but not fibrosis was seen in this cohort with substantial improvements post-surgery.

scholarly journals Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiake Yu ◽  
Hu Zhang ◽  
Liya Chen ◽  
Yufei Ruan ◽  
Yiping Chen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Healthy Children ◽  
Nonalcoholic Fatty Liver ◽  
Secondary Bile Acids

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.

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