A low protein diet drives short-and long-term improvements in metabolic health in a mouse model of sleeve gastrectomy

Despite the largely beneficial impact of bariatric surgery on obesity and metabolic disease, continued post-surgical obesity and weight recurrence is common and may be impacted by diet. While guidelines recommend a high-protein diet based on the theory that this will preserve lean mass, emerging evidence suggests that both humans and mice are metabolically healthier on low protein diets. We assessed the effect of varying dietary protein levels on post-surgical weight loss and weight regain in a mouse model of one type of bariatric surgery, sleeve gastrectomy. We found that a low protein diet optimally drives post-surgical weight loss, boosting energy expenditure and improving blood glucose regulation. Using a multi-omics approach, we identified clusters of differentially expressed genes and metabolites that correlated with these phenotypes and found that diet heavily influences the liver’s molecular response to sleeve gastrectomy. These results suggest that current post-surgical high protein guidelines may limit both the short-and long-term benefits of surgery, and a low protein diet may improve patient outcomes.