Tamoxifen-Prefabricated Beige Adipose Tissue Improves Fat Graft Survival in Mice.

Abstract

Fat grafting has become an important tool for breast reconstruction in breast cancer patients. Tamoxifen, the hormone therapy agent most frequently used for breast cancer, can affect adipose metabolism and cause browning of adipose tissue. This study hypothesized that tamoxifen could increase fat graft survival by altering adipose metabolism. C57/BL6 mice were divided into three groups receiving different treatments before and after fat grafting. The tamoxifen/grafting/tamoxifen group was pretreated with daily tamoxifen for 8 weeks, received fat grafting, and was treated with daily tamoxifen. The graft/tamoxifen group was pretreated with daily phosphate-buffered saline for 8 weeks, received fat grafting, and was treated with daily tamoxifen. The control group was pretreated with daily phosphate-buffered saline for 8 weeks, received fat grafting, and was treated with daily phosphate-buffered saline. The inguinal fat used for transplantation and the transferred fat at weeks 4 and 12 after transplantation were harvested and analyzed. Tamoxifen-pretreated inguinal fat showed beige fat features, with smaller adipocyte size, up-regulated uncoupling protein 1 expression, and improved vascularization. The retention rate of transferred fat was significantly higher in the tamoxifen/grafting/tamoxifen group than in the control group (69 ± 12 percent versus 36 ± 13 percent; p < 0.05), but fat grafts in the graft/tamoxifen group had a retention rate similar to that in the control group (31 ± 12 percent versus 36 ± 13 percent; p > 0.05). Improved angiogenesis and increased vascular endothelial growth factor expression were found in the tamoxifen/grafting/tamoxifen group but not in the graft/tamoxifen group. Tamoxifen treatment before fat grafting resulted in prefabricated vascularized beige fat with small adipocytes, which greatly improve fat graft survival. However, tamoxifen after fat grafting did not affect fat graft evolution.