Browning of White Adipocytes in Fat Grafts Associated with Higher Level of Necrosis and Type 2 Macrophages Recruitment.

BACKGROUND Induced browning adipocytes were assumed less viable and more prone to necrosis for their hypermetabolic property. Our previous study showed that browning of adipocytes was more evident in fat grafts with necrosis in humans. OBJECTIVES We aimed to estimate whether fat-transfer-induced browning biogenesis was associated with necrosis and its potential inflammation mechanisms in murine models. METHODS Human subcutaneous adipose from thigh or abdomen of 5 patients via liposuction were injected in 100µl or 500µl (n=20 per group) into the dorsal flank of 6-8-week female nude mice fed with normal chow diet, and harvested after 2, 4, 8 and 12 weeks. Control groups did not receive any grafting procedures (sham operation), where lipoaspirates were analyzed immediately after harvest. Histology and electronic microscopy, immunological analyses of browning markers, necrosis marker, and type I/II macrophages markers in mice were performed. RESULTS Histology and electronic microscopy showed browning adipocytes in in fat grafts with higher level of necrosis (0.435±0.017pg/ml for cleaved caspase-3, **p<0.01), IL-6(749.0±134.1pg/ml,***p<0.001) and infiltration of type 2 macrophage profiles in mice(2-fold increase, *p<0.05). CONCLUSIONS Browning of adipocytes induced by fat transfer in mice is in parallel with post-grafting necrotic levels, associated with elevated IL-6 and activated M2 macrophages profiles which promote browning development.