Induction of Adipocyte Hyperplasia in Subcutaneous Fat Depot Alleviated Type 2 Diabetes Symptoms in Obese Mice

Objective: The role of subcutaneous adipose tissue (SAT) in the pathogenesis of type 2 diabetes is still under controversy. In this study, the metabolic effects of inducing adipocyte hyperplasia in SAT depots in obese mice were investigated. Methods: High fat diet was used to induce obesity and type 2 diabetes symptoms in C57BL6/J mice. To induce SAT expansion through hyperplasia, acellular adipogenic cocktails were injected around the SAT depots in high fat diet-induced obese mice. Results: Ten weeks after injections, significant neoadipogenesis was induced, which not only obviously expanded the volume of SATs but also significantly increased the adipocyte density within the whole SAT depots. Importantly, these mice exhibited improved glucose tolerance and insulin sensitivity (homeostatic model assessment) when compared to control group. Further studies suggested that these beneficial metabolic effects were associated with elevation of serum high-molecular-weight adiponectin level and reduction of ectopic lipid accumulation in liver. Conclusions: These findings not only further supported the protective role of SAT in the pathogenesis of type 2 diabetes but also highlighted the importance of adipocyte hyperplasia in this protective effect.