Brown adipose tissue transplantation ameliorates hindlimb ischemic damage in diabetic mice

Peripheral arterial disease (PAD) is a common complication associated with diabetes, which can lead to foot ischemia. The condition is often accompanied by infection and necrosis, ultimately leading to diabetic foot ulcers and the risk of amputation. Brown adipose tissue (BAT) and its secreted cytokines play an essential role in the regulation of glucose homeostasis, the modulation of inflammatory responses, and vascular endothelial cell proliferation. The transplantation of BAT into ischemic regions may offer therapeutic benefits in alleviating the symptoms associated with PAD. A diabetic mouse model was established via intraperitoneal administration of streptozocin. Subsequently, a diabetic lower limb ulcer model was constructed by transection of the femoral artery and ligation of the femoral vein. BAT harvested from the subscapular region of the mouse was employed as an adipose graft. The research utilized Laser Doppler monitoring, Western blot analysis, hematoxylin-eosin (HE) staining, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA) to evaluate blood flow recovery in ischemic regions, histopathological changes, angiogenesis and tissue remodeling, inflammatory responses, and M1/M2 macrophage polarization. BAT transplantation significantly enhanced blood flow recovery in ischemic regions of diabetic lower limb ulcer mice while concurrently reducing necrotic tissue. Pathological analyses demonstrate that BAT transplantation mitigates ischemic tissue damage, stimulates angiogenesis, and supports tissue remodeling. Furthermore, the Western blotting, immunofluorescence, and ELISA results revealed that BAT transplantation significantly reduces inflammatory levels in ischemic tissues, increases the expression of angiogenic factors, and promotes the polarization of macrophages from the M1 to the M2 phenotype. The research has demonstrated that BAT transplantation can mitigate ischemic injury in diabetic lower limb ulcer mice, attenuate inflammatory responses, and facilitate the restoration of blood flow. These effects may be linked to alterations in macrophage polarization.