At a Glance
Obesity and related diseases like Type 2 diabetes, liver disease and heart disease have become major health concerns in Wisconsin. Bariatric surgery, especially sleeve gastrectomy, is the most effective long-term treatment, often resulting in significant weight loss. However, many patients eventually hit a weight-loss plateau. Using mouse and pig models, this study aims to better understand how protein intake influences recovery and long-term outcomes after surgery, with the potential to develop new diet-based therapies for people with obesity and related diseases.
The Challenge
Bariatric surgery is the most effective long-term treatment for obesity and related diseases, often resulting in substantial improvements in weight and health. However, metabolic adaptations to surgery tend to plateau within two years of the operation, leaving patients with significant residual weight and continued metabolic disease. There is the potential to dramatically impact the response to surgery through postoperative diet. Recently, protein restriction has been shown to induce weight loss, improve metabolic health, and extend lifespan in mice and humans.
Project Goals
This research team seeks to address two major knowledge gaps in the understanding of sleeve gastrectomy and postoperative metabolism. The aims of this project are to:
- Define the impact of sleeve gastrectomy and postoperative diet on intestinal enteroendocrine cell biology, hormone production, and downstream pancreatic islet function
- Define the impact of protein restriction therapy on metabolism in a human-like swine model of obesity
Progress Update
The research team has made significant progress in the first year. Diet-induced obese mice were randomized to a sham treatment or vertical sleeve gastrectomy (VSG) followed by either high or low protein diets. The researchers longitudinally tracked weight, body composition, and glucose tolerance. Data showed that the impact of VSG is heavily influenced by postoperative diet. VSG mice on the low protein diet had the most weight loss, least amount of weight recurrence, and best insulin tolerance. The research team also showed that diet can change intestinal physiology and incretin response to meals.
The research team has completed one of two pilots in Wisconsin Mini Swine. Male and female swine were preconditioned on an obesity-inducing diet for 12 weeks before randomization to a high or low protein diet. While there were no noticeable differences in body composition between groups, there was a trend towards reduced overall adiposity and improved glucose tolerance in the low protein fed swine. The work will continue with a larger second cohort of animals to address study limitations.
