Sleeve Gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss

ABSTRACT Objective Sleeve gastrectomy (SG) induces weight-loss independent improvements in glucose homeostasis by unknown mechanisms. We sought to identify the metabolic adaptations responsible for these improvements. Methods Non-obese C57Bl6/J mice on standard chow underwent SG or sham surgery. Functional testing and indirect calorimetry were used to capture metabolic phenotypes. Tissue-specific glucose uptake was assessed by 18-FDG PET/CT and RNA sequencing was used for gene expression analysis. Results In this model, SG induced durable improvements in glucose tolerance despite not causing lasting changes in weight, fat/lean mass, or food intake. Indirect calorimetry revealed post-SG animals had respiratory exchange ratios (RER) nearing 1.0 on average and had daily RER excursions above 1.0, indicating preferential glucose utilization and increased energy demand, respectively. Sham operated mice demonstrate normal RER feeding/fasting excursions. PET/CT showed increased avidity within white adipose depots. Finally, SG led to an upregulation in the transcriptional pathways involved in energy metabolism, adipocyte maturation, and adaptive and innate immune cell chemotaxis and differentiation within the visceral adipose tissue. Conclusions SG induces a rapid, weight-loss independent shift towards glucose utilization and transcriptional remodeling of metabolic and immune pathways in visceral adipose tissue.