Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

Noël, Olivier; Still, Christopher D.; Argyropoulos, George; Edwards, Michael A.; Gerhard, Glenn S.

doi:10.1155/2016/4390254

Cited by 43 publications

(30 citation statements)

References 85 publications

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“…1,[36][37][38] Several mechanisms may account for the elevation of PYY in islets after bariatric surgery, including changes in bile acids and microbiota-derived metabolites. Quantitative and qualitative modification of these factors has been well documented post gastric bypass in rodents and humans [39][40][41][42] and, in some cases, they have been shown to directly regulate PYY expression in gut cells. 43,44 Whether PYY content in islets is also affected by these factors remains an interesting avenue to explore.…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Guida

McCulloch

Godazgar

et al. 2017

Diabetes Obesity Metabolism

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AimsThe gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux‐en‐Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme dipeptidyl peptidase IV (DPP‐IV) has not been investigated and the impact of DPP‐IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose‐stimulated insulin secretion (GSIS). We have also investigated changes in pancreatic PYY in diabetes and following RYGB.MethodsImmunohistochemistry and gene expression analysis were used to assess PYY, NPYRs and DPP‐IV expression in rodent and human islets. DPP‐IV activity inhibition was achieved by sitagliptin. Secretion studies were used to test PYY and the effects of sitagliptin on insulin release, and the involvement of GLP‐1. Radioimmunoassays were used to measure hormone content in islets.ResultsPYY and DPP‐IV localized in different cell types in islets while NPYR expression was confined to the beta‐cells. Chronic PYY application enhanced GSIS in rodent and diabetic human islets. DPP‐IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally‐produced PYY, and not GLP‐1. Pancreatic PYY was markedly reduced in diabetes. RYGB strongly increased islet PYY content, but did not lead to full restoration of pancreatic GLP‐1 levels.ConclusionLocal regulation of pancreatic PYY, rather than GLP‐1, by DPP‐IV inhibition or RYGB can directly modulate the insulin secretory response to glucose, indicating a novel role of pancreatic PYY in diabetes and weight‐loss surgery.

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Section: Discussionmentioning

confidence: 99%

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Guida

McCulloch

Godazgar

et al. 2017

Diabetes Obesity Metabolism

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“…Its role will only be briefly mentioned in this article. Bariatric surgery increases BA levels, changes BA composition, decreases hepatic steatosis, and improves insulin resistance (Bhutta et al, 2015; Dutia et al, 2015; Myronovych et al, 2014; Noel et al, 2016). SHP is also believed to play a role in preventing liver inflammation after sleeve gastrectomies (Myronovych et al, 2014).…”

Section: Current Therapiesmentioning

confidence: 99%

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Chow

Lee

Guo

2017

Molecular Aspects of Medicine

119

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Nonalcoholic fatty liver disease is growing in prevalence worldwide. It is started by the presence of macrosteatosis on liver histology but is often clinically asymptomatic. However, it can progress into nonalcoholic steatohepatitis which is a more severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism by which simple steatosis progresses to steatohepatitis is not entirely clear. However, multiple pathways have been proposed. A common link amongst many of these pathways is disruption of the homeostasis of bile acids. Other than aiding in the absorption of lipids and lipid-soluble vitamins, bile acids act as ligands. For example, they bind to farnesoid X receptor, which is critically involved in many of the pathways responsible for maintaining bile acid, glucose, and lipid homeostasis. Alterations to these pathways can lead to deregulation in energy balance and increased inflammation and fibrosis. Repeated insults over time may be the key to development of steatohepatitis. For this reason, current drugs target aspects of these pathways to try to reduce and halt inflammation and fibrosis. This review will focus on the role of bile acids in these various pathways and how changes in these pathways may result in steatohepatitis. While there is no approved pharmaceutical treatment for either hepatic steatosis or steatohepatitis, this review will also touch upon the multitude of potential therapies.

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“…Together, these data suggested that FXR is involved in suppression of rebound hyperphagia which would follow VSG and the resultant calorie restriction (10). Subsequently bile acids and FXR have been proposed as key mediators of diabetes resolution and weight loss following bariatric surgery (12).…”

Section: Introductionmentioning

confidence: 93%

Farnesoid X receptor ‐ a molecular predictor of weight loss after vertical sleeve gastrectomy?

Scott

Elahi

Adebibe

et al. 2019

Obesity Science & Practice

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Summary Objective To determine the expression of the bile acid receptor, farnesoid X (FXR), in human gastric mucosa and investigate correlations between expression and body‐mass index (BMI) and in patients with obesity, with changes in weight and BMI following vertical sleeve gastrectomy (VSG). Methods Human gastric mucosa was obtained from normal/overweight individuals (macroscopically‐normal tissue following surgery for malignancy) or from patients with obesity (VSG). The expression of FXR and its isoforms (FXRα, FXRβ) were examined by quantitative PCR and compared with the G protein‐coupled bile acid receptor, GPBA. In patients with obesity, changes in BMI and weight loss were determined following VSG. Results FXRα was the predominant isoform in normal/overweight individuals. FXR expression was higher in patients with obesity but GPBA receptor expression was unchanged. For those with obesity ( n = 19), no correlation was found between FXR expression and change in Body‐Mass Index (BMI)/month or weight loss/month, taken 3 ± 1 months after surgery, or in BMI or weight at surgery. Conclusions Obesity is associated with increased FXR expression in the gastric mucosa. The findings are preliminary but suggest that this increase in FXR expression is a consequence of obesity, rather than its cause.

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Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

Cited by 43 publications

References 85 publications

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

Sitagliptin and Roux‐en‐Y gastric bypass modulate insulin secretion via regulation of intra‐islet PYY

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Farnesoid X receptor ‐ a molecular predictor of weight loss after vertical sleeve gastrectomy?

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