Roux-en-Y gastric bypass alters small intestine glutamine transport in the obese Zucker rat.
The metabolic effects of Roux-en-Y gastric bypass (RYGB) are caused by postsurgical 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 present study examines the effects of obesity and RYGB on intestinal glutamine transport and metabolism. First, lean and obese Zucker rats (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 postoperative day 28. Glutamine transporter activity and abundance, B(0)AT1 protein, and mRNA levels were measured. Levels of glutaminase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), and glucose-6-phosphatase (G6Pase) were measured to assess glutamine metabolism and intestinal gluconeogenesis. Obesity increased glutamine transport and B(0)AT1 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 B(0)AT1 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-C and G6Pase were decreased in all segments of intestine after RYGB. RYGB selectively increased glutamine absorption in biliopancreatic and Roux limbs by a mechanism involving increased B(0)AT1 expression. Post-RYGB glutaminase levels were increased, but the reductions in PEPCK-C and G6Pase suggest that RYGB downregulates intestinal gluconeogenesis.
Wolff
Brynn S
BS
Department of Surgery, Penn State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033-0850, USA.
Meirelles
Katia
K
Meng
Qinghe
Q
Pan
Ming
M
Cooney
Robert N
RN
D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004195:Disease Models, Animal; D015390:Gastric Bypass; D005943:Gluconeogenesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000601:surgery*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015854:Up-Regulation
D026921:Amino Acid Transport Systems, Neutral; D012333:RNA, Messenger; C520324:SLC6A19 protein, rat; D005973:Glutamine; D005952:Glucose-6-Phosphatase; D005972:Glutaminase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)