A surgical mouse model to study intestinal plasticity and weight-loss

Bariatric Surgery is clinically the most effective method to achieve sustained weight loss in the battle against obesity. It is established that bariatric surgeries have additional beneficial effects on metabolic diseases, such as diabetes, fatty liver and cardiovascular complications. Mini gastric bypass is an aggressive malabsorptive bariatric surgery leading to substantial reduction in weight. In this surgery, the stomach is bisected near the antrum, and the distal jejunum is anastomosed to the body of the stomach. Therefore, the antrum, duodenum and proximal jejunum, comprising nearly half of the intestine, are bypassed.

We report here the generation of a mouse model of the surgery. Obese C57/bl6 male mice were operated after 35 weeks on a high fat diet. Even though the mice were kept on the same diet, they lost approx. 25% of their initial weight and were 40% leaner than their sham operated littermates. Similar to human patients, they display improved glycemic control and liver steatosis. Metabolic cage analysis indicates that the mice have altered energy expenditure compared with pair fed mice or mice that have undergone vertical sleeve gastrectomy. We also observe macroscopic and microscopic adaptations of both bypassed and food bearing jejunum to the new anatomy compared with sham operated controls. We conclude that the mouse mini gastric bypass is a useful model to understand the effects of this surgery. Furthermore, it is a new and unique model to study the molecular mechanisms underlying the adaptation of the gastrointestinal tract to extreme nutritional challenges.