Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery

Albaugh, Vance L.; Banan, Babak; Antoun, Joseph; Xiong, Yanhua; Guo, Yan; Ping, Jie; Alikhan, Muhammed Mustafa; Clements, Blake Austin; Abumrad, Naji N.; Flynn, Charles R.

doi:10.1053/j.gastro.2018.11.017

Cited by 126 publications

(111 citation statements)

References 69 publications

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“…44,48 In BD surgery, the gallbladder is anastomosed to the ileum and the bile duct is ligated to divert BAs further down the intestinal tract, increasing BA reabsorption and shortening enterohepatic circulation time, which functionally results in elevated systemic BAs. 44,48,49 In obese animals, BD surgery improved obesity-driven components of metabolic syndrome with no adverse malabsorptive effects on fecal lipid or BA excretion but this depends on location of anastomosis to the ileal cecal valve. 44,49 Pierre et al reported that BD led to sustained weight loss, reduced adiposity to lean levels, and normalized glucose tolerance by 2 weeks after surgery.…”

Section: Ob E S It Y Bariatri C Surg Ery-induced Wei G Ht Loss Amentioning

confidence: 99%

“…44,48,49 In obese animals, BD surgery improved obesity-driven components of metabolic syndrome with no adverse malabsorptive effects on fecal lipid or BA excretion but this depends on location of anastomosis to the ileal cecal valve. 44,49 Pierre et al reported that BD led to sustained weight loss, reduced adiposity to lean levels, and normalized glucose tolerance by 2 weeks after surgery. 44,48 Strikingly, BD surgery resulted in sustained weight loss despite continued high-fat diet exposure.…”

Section: Ob E S It Y Bariatri C Surg Ery-induced Wei G Ht Loss Amentioning

confidence: 99%

“…Pierre and others further reported that FXR is critical for BAR-mediated metabolic improvements after BD-induced weight loss using FXR deficient mice. 48,49 Specific microbes may also mediate some beneficial effects of metabolic surgery. After BD, Firmicutes were decreased and Bacteroidetes were increased.…”

Section: Ob E S It Y Bariatri C Surg Ery-induced Wei G Ht Loss Amentioning

confidence: 99%

See 2 more Smart Citations

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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Bile acids (BAs) are known facilitators of nutrient absorption but recent paradigm shifts now recognize BAs as signaling molecules regulating both innate and adaptive immunity. Bile acids are synthesized from cholesterol in the liver with subsequent microbial modification and fermentation adding complexity to pool composition. Bile acids act on several receptors such as Farnesoid X Receptor and the G proteincoupled BA receptor 1 (TGR5). Interestingly, BA receptors (BARs) are expressed on immune cells and activation either by BAs or BAR agonists modulates innate and adaptive immune cell populations skewing their polarization toward a more tolerogenic anti-inflammatory phenotype. Intriguingly, recent evidence also suggests that BAs promote anti-tumor immune response through activation and recruitment of tumoricidal immune cells such as natural killer T cells. These exciting findings have redefined BA signaling in health and disease wherein they may suppress inflammation on the one hand, yet promote anti-tumor immunity on the other hand. In this review, we provide our readers with the most recent understanding of the interaction of BAs with the host microbiome, their effect on innate and adaptive immunity in health and disease with a special focus on obesity, bariatric surgery-induced weight loss, and immune checkpoint blockade in cancer. K E Y W O R D S bariatric surgery, immunometabolism, microbiome, mitochondria, obesity, tumor microenvironment | 221 SIPE Et al.

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Section: Ob E S It Y Bariatri C Surg Ery-induced Wei G Ht Loss Amentioning

confidence: 99%

Section: Ob E S It Y Bariatri C Surg Ery-induced Wei G Ht Loss Amentioning

confidence: 99%

Section: Ob E S It Y Bariatri C Surg Ery-induced Wei G Ht Loss Amentioning

confidence: 99%

See 1 more Smart Citation

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Sipe

Chaib

Pingili

et al. 2020

Immunological Reviews

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“…Interestingly, diversion of bile from the proximal to the distal small intestine was shown to induce comparable weight loss and metabolic benefits to Roux‐en‐Y gastric bypass in rodents, consistent with the concept that bile acids have a major role in mediating the metabolic benefits of bariatric surgery. Moreover, in rodent models of obesity the benefits of biliary diversion are attenuated in the presence of exendin (9‐39), and in GLP‐1 receptor null mice, attesting to the importance of GLP‐1 . Accordingly, the delivery of bile acids to the distal gut, without the need for surgery, may potentially be beneficial in the management of T2DM.…”

Section: Gastrointestinal Effects Of Metformin: Role Of Gut Peptidesmentioning

confidence: 99%

Mechanism of glucose‐lowering by metformin in type 2 diabetes: Role of bile acids

Sansome

Xie

Veedfald

et al. 2019

Diabetes Obesity Metabolism

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Type 2 diabetes mellitus (T2DM) is an increasingly prevalent chronic condition, characterized by abnormally elevated blood glucose concentrations and, as a consequence, increased risk of micro‐ and macrovascular complications. Metformin is usually the first‐line glucose‐lowering medication in T2DM; however, despite being used for more than 60 years, the mechanism underlying the glucose‐lowering action of metformin remains incompletely understood. Although metformin reduces hepatic glucose production, there is persuasive evidence that the gastrointestinal tract is crucial in mediating this effect, particularly via secretion of the incretin hormone glucagon‐like peptide 1 (GLP‐1). It is now well recognized that bile acids, in addition to their established function in fat digestion and absorption, are important regulators of glucose metabolism. Exposure of the small and large intestine to bile acids induces GLP‐1 secretion, modulates the composition of the gut microbiota, and reduces postprandial blood glucose excursions in humans with and without T2DM. Metformin reduces intestinal bile acid resorption substantially, such that intraluminal bile acids may, at least in part, account for its glucose‐lowering effect. The present review focuses on the conceptual shift in our understanding as to how metformin lowers blood glucose in T2DM, with a particular emphasis on the role of intestinal bile acids.

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“…We have shown that bile acids are increased after VSG and that FXR is essential for the positive effects of bariatric surgery on weight loss and glycemic control Ryan et al, 2014). Unlike wild-type mice, FXR-/-mice do not maintain body weight loss and do not have improved glucose tolerance after VSG or after bile diversion to the ileum (Albaugh et al, 2019;Ryan et al, 2014). These studies have highlighted the importance of the enterohepatic circulation in the metabolic effects following bariatric surgery.…”

Section: Introductionmentioning

confidence: 99%

Intestinal-derived FGF15 preserves muscle and bone mass following sleeve gastrectomy

Bozadjieva-Kramer

Shin

Shao

et al. 2020

Preprint

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Bariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive, but provide the most effective long-term metabolic improvements in obese and Type 2 diabetic patients. These powerful effects of manipulating the gastrointestinal tract point to an important role of gastrointestinal signals in regulating both energy balance and metabolism. To that end, we have used mouse models of VSG to identify key gut signals that mediate these beneficial effects. Preliminary data from our rodent model of VSG led us to hypothesize a potential role for the hormone Fibroblast-Growth Factor15/19 (mouse/human ortholog) which pharmacologically can regulate many aspects of energy homeostasis and glucose handling. FGF15 is expressed in ileal enterocytes of the small intestine and is released postprandially. Like many other gut hormones, postprandial plasma levels in humans and ileal FGF15 expression in mice increase after VSG. We generated intestinal-specific FGF15 knock out (VilCreERT2;Fgf15 f/f ) mice and controls, which were maintained on 60% high-fat diet. Interestingly, ablation of intestinal FGF15 in adult mice results in little change to body weight or glucose regulation when challenged with a high-fat diet. Unlike what we had predicted, intestinal-specific FGF15 knock out mice lost more weight after VSG and this was a result of increased lean tissue loss compared to control mice. Further, the loss of bone mineral density observed after VSG in control mice was increased in intestinal-specific FGF15 knock out mice. Finally the effect of VSG to reduce hepatic cholesterol was also absent in intestinal-specific FGF15 knock out mice. These data point to an important role for intestinal FGF15 to protect the organism from deleterious effects of rapid weight loss that occurs after VSG.

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Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery

Cited by 126 publications

References 69 publications

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

Mechanism of glucose‐lowering by metformin in type 2 diabetes: Role of bile acids

Intestinal-derived FGF15 preserves muscle and bone mass following sleeve gastrectomy

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