Elevated GLP-1 Levels After Roux-en-Y May Affect Responsiveness to Food Cues

A study recently published in Diabetes Care investigated the effects of is Roux-en-Y gastric bypass surgery (RYGB) on central nervous system (CNS) activation in response to food cues, measured with functional magnetic resonance imaging (fMRI).

Researchers led by Richard G. Ijzerman of VU Medical Center in Amsterdam, the Netherlands, point out that it has been suggested that weight reduction and improvements in satiety after RYGB are partly mediated via postoperative changes in the CNS and endocrine system. Glucagon-like peptide-1 (GLP-1), is associated with diminishing appetite and weight reduction. Secretion of GLP-1 is greatly enhanced after RYGB. “We hypothesized that postoperative elevated GLP-1 levels contribute to the improved satiety regulation after RYGB via effects on the CNS,” the authors write.

Ten female candidates for laparoscopic RYGB procedures between 40 to 65 years of age were recruited from the Center for Bariatric Surgery in the Netherlands. The patients met the study’s weight and health guidelines, and they each had a body mass index greater than 35 kg/m2. The study consisted of four separate patient test visits. Effects of the GLP-1 receptor antagonist exendin 9-39 (Ex9- 39), which is used to block effects of endogenous GLP-1, and a placebo were assessed before and after RYGB using fMRI to investigate CNS activation in response to visual food cues (pictures) and gustatory food cues (consumption of chocolate milk). The results indicated that RYGB was consistently associated with increased postoperative levels of GLP-1, and RYGB also decreased activation in feeding regulation areas in the CNS in response to food stimuli.

The effect of Ex9-39 on GLP-1 levels and CNS responses to both the viewing of food pictures and the consumption of palatable food was larger after RYGB compared with before surgery, suggesting that these effects of RYGB may be partly explained by postoperative changes in the levels of endogenous GLP-1 and/or possible changes in sensitivity to GLP-1. These findings provide further insights in the weight lowering mechanisms of RYGB and the sustained efficacy of this procedure, and may ultimately lead to further development of treatment strategies for obesity.