Objectives: Increased energy expenditure (EE) has been proposed an important mechanism for weight loss following Roux-en-Y gastric bypass (RYGB). However, this has never been investigated in a controlled setting independent of changes in energy balance. Likewise, only few studies have investigated the effect of RYGB on glycaemic control per se. Here, we investigated the effect of RYGB on EE, appetite, glycaemic control, and specific signalling molecules compared to a control group in comparable negative energy balance.

Subjects/Methods: Obese normal glucose tolerant participants were randomized to receive RYGB after 8 (n=14) or 12 weeks (n=14). The protocol included a visit at week 0 and three visits (week 7, 11 and 78) where 24 h EE, appetite and blood parameters were assessed. Participants followed a low-calorie diet from week 0-11, with those operated at week 12 serving as a control group for those operated at week 8.

Results: Compared to controls, RYGB operated participants had lower body composition-adjusted 24 h EE and basal EE three weeks postoperatively (both P<0.05) but EE parameters at week 78 were not different from pre-operative values (week 7). Surgery changed the postprandial response of GLP-1, PYY, ghrelin, CCK, FGF-19 and bile acids (all P<0.05). Particularly, increases in GLP-1, PYY and decreases in ghrelin were associated with decreased appetite. None of HOMA-IR, Matsuda Index, the Insulinogenic Index, the Disposition Index and fasting hepatic insulin clearance were different between the groups, but RYGB operated had lower fasting glucose (P<0.05) and the postprandial glucose profile was shifted to the left (P<0.01).

Conclusion: Our data do not support that EE is increased after RYGB. More likely, RYGB promotes weight loss by reducing appetite, partly mediated by changes in gastrointestinal hormone secretion. Furthermore, we found that the early changes in glycaemic control after RYGB is to a large extent mediated by caloric restriction.