Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin-Sensitizing, Secondary Bile Acids

Abstract

Overall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.

Bile acids and bariatric surgery

“…We (Isbell et al, 2010) and others (Kashyap et al, 2010; Laferrère et al, 2007; le Roux et al, 2007; Morínigo et al, 2006a) have described large increases in postprandial GLP-1 immediately after RYGB that are sustained in the long-term (Bose et al, 2010; Morínigo et al, 2006a; 2006b; Vidal et al, 2009). Intriguingly, the increased GLP-1 at one month post-operative coincides with significant increases in total bile acids (Albaugh et al, 2015). As the complex physiology of metabolism and body weight regulation is increasingly appreciated, contributions of both the foregut and hindgut hypotheses are likely at work in these patients and experimental models, though the search for a particular factor linking each of these hypotheses continues to be sought.…”

“…It is clear from the literature that there are fundamental differences in bile acid metabolism regulated by total body adiposity between lean and obese individuals independent of insulin resistance. Several groups have shown decreased circulating concentrations of bile acids in obesity relative to leans (Albaugh et al, 2015; Cariou et al, 2011), though others suggest that insulin resistance drives increased bile acid synthesis and circulating bile acids (Haeusler et al, 2015; Sun et al, 2016). In addition to increasing synthesis and pool size, insulin resistance is associated with altered bile acid composition, specifically increased abundance of 12α-hydroxylated bile acid species which may be important negative regulators of insulin action (Haeusler et al, 2013).…”

“…One interventional study showed that 6 weeks of oral tauro-ursodeoxycholic acid, a bile acid that has been shown to be elevated early after RYGB (Albaugh et al, 2015), improves hepatic and skeletal muscle insulin sensitivity in obese, insulin resistant subjects without frank diabetes (Kars et al, 2010). Animal models have suggested numerous off-target effects of ursodeoxycholic acid (UDCA), including alleviation of endoplasmic reticulum stress (Özcan et al, 2006; Roma et al, 2011), augmented glucose-stimulated insulin secretion (Düfer et al, 2012) and augmentation of the incretin effect through GLP-1 and potentially other incretin hormones (Rafferty et al, 2011), though data in humans are limited (Murakami et al, 2013).…”

Cholesterol 7α-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders

“…Manipulations of the bile acid pool size by bile acid supplementation, bile acid sequestrants, or pharmacological activation of FXR and TGR5 signaling have been shown to improve insulin sensitivity and glucose tolerance in mouse models of diabetes and obesity and in nonalcoholic steatohepatitis patients (11)(12)(13). Bile acids also have been implicated in rapidly improving insulin resistance in type 2 diabetic patients after bariatric surgery and in animal models (14)(15)(16).…”

Obesity diabetes and the role of bile acids in metabolism

“…At 24 months, there was an increase in both primary unconjugated bile acids as well as secondary deoxycholate conjugated with glycine. The authors suggest that the changes were bacterially derived [27] .…”