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

Despite the beneficial impact of bariatric surgery on obesity and metabolic disease, continued post-surgical obesity and weight recurrence are common, but may be impacted by diet. While guidelines recommend a post-operative high-protein diet to preserve lean mass, emerging evidence suggests that humans and mice are metabolically healthier on low-protein diets. Here, we assess the effect of varying dietary protein on post-surgical metabolism in a mouse model of sleeve gastrectomy. We find that a low-protein diet optimally drives post-surgical weight loss, boosts energy expenditure, and improves blood glucose regulation, likely, in part, due to the induction of FGF21. Through multi-omics, we identified clusters of differentially expressed genes and metabolites that correlate with these phenotypes and find that diet heavily influences the liver's molecular response to sleeve gastrectomy. These results suggest that current post-surgical high-protein diets may limit the short- and long-term benefits of surgery and warrant human clinical trials.