Abstract

We investigated whether metabolic phenotype improvements following gastric bypass are associated with gastric resection strategy in high-fat diet-induced obese (DIO) mice. We developed the mouse Roux-en-Y gastric bypass (RYGB) model with different gastric pouch sizes: (i) RYGB with a large gastric pouch (RYGB-LP), where the stomach was transected, and the jejunum was anastomosed to the residual forestomach, in which 30% of the stomach is retained. (ii) RYGB with a small remnant gastric pouch (RYGB-SP), where the stomach was transected 0.8cm distal to the esophagogastric junction, and the jejunum is attached to a small remnant of the forestomach (~ 10% of the stomach). (iii) RYGB without gastric pouch (RYGB-NP), where the jejunum is anastomosed to the lower portion of the esophagus. Surgical success rate (or 4-week mouse survival rate) of the RYGB-LP, RYGB-SP, and RYGB-NP procedures was 50, 75, and 85%, respectively. Our data demonstrate that all RYGB procedures improved body weight, glucose tolerance, and liver steatosis, compared with untreated DIO mice at 8-week post-surgery. Major surgical complication, such as obstruction at the forestomach, occurred predominantly in RYGB-LP mice, resulting in a higher mortality. Pre- and post-prandial plasma ghrelin levels did not correlate with improved metabolic phenotype after gastric bypass. We conclude that RYGB with different gastric pouch equally improves obesity and glucose tolerance independent of gastric pouch size and total plasma ghrelin levels in the mouse model of RYGB surgery.

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