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The Role of Complete and Partial Gastric Bypass in Determining the Efficacy of Bariatric Surgery in the Mouse

Dengping Yin (Chicago, IL)

MICROMouse Program

Clinical data and research efforts have clearly shown that diabetes control by bariatric surgery is not simply a matter of the mechanical perturbation of the gastrointestinal (GI) tract or restrictive dietary intake but involves biological mechanisms that are not yet understood. The advantage of establishing bariatric surgery procedures in mice pertains to the vast number of genetic mouse models available to study the mechanisms by which different foregut bypass procedures influence metabolic, neuroendocrine and immunological subsequences. However, most of bariatric surgery mouse models limit in duodenal-jejunal bypass (DJB). There is a very limited understanding whether stomach exclusion or duodenal bypass is sufficient to improve glucose homeostasis and insulin action. We have created mouse Roux-en-Y gastric bypass (RYGB) model in which the stomach is excluded and nutrients completely bypass the stomach, which differs from the human RYGB procedure where a portion of the stomach is retained. In the proposed study, we will perform a novel foregut bypass procedure in which a portion of the stomach is retained in nutrient passage to mimic the RYGB procedure conducted in patients, compared to our established RYGB model. A DJB model in which the entire stomach is preserved and nutrients fully mix with gastric secreta will be established. The different bariatric surgeries that are currently used in the clinic and research result in different alterations in GI anatomy, which will affect the metabolic signaling, enteroendocrine action, immunological changes and central nerve system homeostatic circuits with different fashions. The experiments outlined in this pilot project will be able to identify the regulatory effects of foregut bypass with/without exclusion of the stomach in weight loss, insulin action and glucose homeostasis. This project will be completed in one year.

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