Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), is currently the most effective treatment for obesity and often results in type 2 diabetes resolution and possibly type 2 diabetes prevention

Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), is currently the most effective treatment for obesity and often results in type 2 diabetes resolution and possibly type 2 diabetes prevention (Buchwald et al., 2004; Cummings et al., 2010c; Schauer et al., 2012; Sjöström et al., 2004). However, the mechanisms (beyond body weight reduction) responsible for these effects remain undefined. Although gastric restriction and malabsorption probably contribute to maintenance of long-term weight loss, there is increased interest in the role of endocrine and metabolite changes in the effects of bariatric surgery to induce weight loss and prevent diabetes onset (Scott and Batterham, 2011; Thaler and Cummings, 2009). In particular, post-operative elevations in circulating bile acids have become an increasingly cited mechanism for the metabolic benefits of bariatric surgeries, such as RYGB and vertical sleeve gastrectomy (Cummings et al., 2012; Patti et al., 2009; Thaler and Cummings, 2009). RYGB produces several post-operative alterations in normal GI anatomy and function, such as reduction in gastric volume, bypass of the proximal small intestine and increased flux of incompletely absorbed nutrients and bile into the distal small intestine. By contrast, ileal interposition (IT) surgery only involves transposition of a segment of distal small intestine into the proximal jejunum. Thus, the only major change produced by this surgery is increased flux of incompletely absorbed nutrients and bile to the distal small intestine (Strader, 2006). By investigating the effects of only one of the anatomical alterations produced by RYGB in isolation, we can better assess mechanisms by which this component of bariatric surgery improves glucose metabolism. Plasma bile acids are elevated after bariatric surgeries such as RYGB and IT surgery in rodents and clinical studies in humans and have been suggested to have a role in producing the metabolic benefits observed after these types of bariatric surgery (Kohli et al., 2010; Nakatani et al., 2009; Patti et al., 2009). However, the mechanisms by which post-operative increases in circulating bile acid concentrations contribute to the metabolic benefits of bariatric