A Role for Wnt Signaling in the Reversal of Metabolic Disturbances after Gastric Bypass in Obese Mice

Gastric bypass surgery has benefi cial effects on obesity-induced metabolic disturbances, but the underlying mechanisms remain unclear. As Wnt genes are both positively and negatively correlated with obesity-induced adipose tissue infl ammation and insulin resistance, our main aim is to reveal a potential role for Wnt signaling in the reversal of these metabolic consequences after gastric bypass surgery in mice. 8-weeks old male C57Bl/6 mice were fed a high fat diet (60 kcal% fat) for 14 weeks, followed by either Roux-en-Y gastric bypass (RYGB; n=13) or Sham surgery (Sham; n=10). After surgery, mice were maintained on a high fat diet for another 8 weeks (Sham group was pair fed with the RYGB group). Using qRT-PCR, the mRNA expression profi le of Wnt ligands and its antagonists (i.e. secreted Frizzled-related proteins (sFRP)) was determined in epididymal white adipose tissue of RYGB and Sham mice. 8 weeks post-surgery, Sham mice returned to their pre-surgery weight (43.4 g ± 6.9), whereas RYGB mice showed a 43% reduction in body weight, accompanied by improved metabolic parameters, as compared to Sham mice (P < 0.01). Epididymal white adipose tissue of RYGB mice showed a 75% and 94% decrease in sFRP4 and sFRP5 mRNA expression levels respectively as compared to Sham mice (P <0.01). Additionally, a trend towards decreased mRNA expression of Wnt5a and Wnt5b could be detected in RYGB mice as compared to Sham mice (P = 0.1). In conclusion, RYGB surgery strongly reduced the expression level of the secreted Wnt antagonists sFRP4 and sFRP5 in white adipocyte tissue. As secreted proteins are interesting drug targets, a potential role for these secreted proteins in the reversal of metabolic disturbances after RYGB surgery will be studied more in depth. Supported By: FWOG.0857.13