Roux-en-Y Gastric Bypass Surgery-Induced Weight Loss and Metabolic Improvements Are Similar in TGR5-Deficient and Wildtype Mice

BACKGROUND AND PURPOSE: Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective treatments for obesity and type 2 diabetes. Despite this, the mechanisms through which it acts are still not well understood. Bile acid signaling through the transmembrane G-protein-coupled receptor TGR5 has been shown to have significant effects on metabolism and has recently been reported to be necessary for the full effects of vertical sleeve gastrectomy (VSG), a bariatric surgery with similar effects to RYGB. The goal of the current study is therefore to investigate the role of bile acid signaling through TGR5 to see if it is necessary to obtain the full effects of RYGB. METHODS: High-fat diet-induced obese TGR5(−/−) and wildtype mice (WT) were subjected to RYGB, sham surgery, or weight matching (WM) to RYGB mice via caloric restriction. Body weight, body composition, food intake, energy expenditure, glucose tolerance, insulin sensitivity, and liver weight were measured. RESULTS: Although the difference in fat mass 20 weeks after surgery between RYGB and sham-operated mice was slightly reduced in TGR5(−/−) mice when compared to wildtype mice, loss of body weight and fat mass from preoperative levels, reduction of food intake, increase of energy expenditure, and improvement in glycemic control were similar in the two genotypes. Furthermore, improvements in glycemic control were similar in non-surgical mice weight-matched to RYGB. CONCLUSIONS: We conclude that bile acid signaling through TGR5 is not required for the beneficial effects of RYGB in the mouse and that RYGB and VSG may achieve their similar beneficial effects through different mechanisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11695-018-3297-6) contains supplementary material, which is available to authorized users.