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 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 individuals who have never been obese, versus those who have. C57BL/6J DIO male mice, 12-13 weeks of age, were purchased from Jackson Labs and maintained on 60% HFD for an additional 2-4 weeks prior to surgery. Mice were fasted overnight prior to surgery. Animals were anesthetized using isoflurane, and a small laparotomy incision was made in the abdominal wall. The lateral 80% of the stomach along the greater curvature was excised in VSG animals by using an ETS 35-mm staple gun. Sham surgery was performed by the application of gentle pressure on the stomach with blunt forceps for 15 seconds. All mice received one dose of Buprinex (0.1 mg/kg) and Carprofen (5 mg/kg) immediately after surgery. All mice received Carprofen (5 mg/kg) for 3 days after surgery. Animals were placed on DietGel Boost for 3 days after surgery. They were placed back on the pre-operative solid diet (60% HFD) on day 4 post-surgery. Body weight and food intake as well as overall health were monitored daily for the first 7 days after surgery and once weekly until the end of the studies. Semaglutide (0.04 mg/kg) was administered to some sham-operated mice subcutaneously once daily starting at day 1 post-surgery. Animals were sacrificed at two timepoints post-surgery, at 10 days for all groups (timepoint 1), and at 25 days for semaglutide treated animals and at 35 days for sham and VSG animals (timepoint 2). All mice were fasted for 4 hours prior to tissue collection.