Semaglutide and bariatric surgery induce distinct changes in the composition of mouse white adipose tissue

Adipose tissue is a central player in energy balance and glucose homeostasis, expanding in the face of caloric overload in order to store energy safely. If caloric overload continues unabated, however, adipose tissue becomes dysfunctional, leading to systemic metabolic compromise in the form of insulin resistance and type 2 diabetes. Changes in adipose tissue during the development of metabolic disease are varied and complex, made all the more so by the heterogeneity of cell types within the tissue. Here we present detailed comparisons of atlases of murine WAT in the setting of diet-induced obesity, as well as after weight loss induced by either vertical sleeve gastrectomy (VSG) or treatment with the GLP-1 receptor agonist semaglutide. We focus on identifying populations of cells that return to a lean-like phenotype versus those that persist from the obese state, and examine pathways regulated in these cell types across conditions. These data provide a resource for the study of the cell type changes in WAT during weight loss, and paint a clearer picture of the differences between adipose tissue from lean animals that have never been obese, versus those that have. • Atlas of almost 50,000 cells from obese mouse inguinal and epididymal adipose tissue after VSG or semaglutide. • VSG leads to an inflammatory phenotype in the peritoneal compartment compared to sham. • Semaglutide induced weight loss leads to remodeling in adipocytes and other cell types. • Some adipocyte genes revert to a chow-like state after weight loss, while others remain locked in the obese pattern.