Submitted on March 18, 2009
Revised on June 12, 2009
Accepted on June 23, 2009
Roux-en-Y Gastric Bypass (RYGB) Alters Small Intestine Glutamine Transport in the Obese Zucker Rat (ZR)
Brynn S. Wolff1, Katia Meirelles1, Qinghe Meng2, Ming Pan3, and Robert Nickerson Cooney4*
1 Penn State Milton S. Hershey Medical Center/Penn State College of Medicine
2 penn state college of medicine
3 Penn State (Hershey Medical Center)
4 Penn State Milton S Hershey Medical Center
* To whom correspondence should be addressed. E-mail: rcooney{at}hmc.psu.edu.
Background: The metabolic effects of RYGB are caused by post-surgical changes in gastrointestinal anatomy affecting gut function. Glutamine is a critical gut nutrient implicated in regulating glucose metabolism as a substrate for intestinal gluconeogenesis. The current study examines the effects of obesity and RYGB on intestinal glutamine transport and metabolism. Methods: First, lean and obese ZRs were compared. Then, the effects of RYGB and sham surgery with pair-feeding (PF) in obese ZRs were studied. Segments of small intestine (biliopancreatic limb, Roux limb and common channel) mucosa were harvested and brush border membrane vesicles (BBMVs) were isolated on post-operative day 28. Glutamine transporter activity and abundance, B0AT1 protein and mRNA levels were measured. Levels of glutaminase, phosphoenolpyruvate carboxykinase (PEPCK-C) and glucose-6-phosphatase (G6Pase) were measured to assess glutamine metabolism and intestinal gluconeogenesis. Results: Obesity increased glutamine transport and B0AT1 expression throughout the intestine. RYGB increased glutamine transport activity in the biliopancreatic (3.8-fold) and Roux limbs (1.4-fold), but had no effect on the common channel. The relative abundance of B0AT1 mRNA and protein were increased in the biliopancreatic (6-fold) and Roux limbs (10-fold) after RYGB (p<0.05 vs. PF), but not the common channel. Glutaminase levels were increased, whereas the relative abundance of PEPCK and G6Pase were decreased in all segments of intestine after RYGB. Conclusion: RYGB selectively increased glutamine absorption in biliopancreatic and Roux limbs by a mechanism involving increased B0AT1 expression. Post-RYGB glutaminase levels were increased, but the reductions in PEPCK and G6Pase suggest RYGB down-regulates intestinal gluconeogenesis.
