Induced Beige Adipocytes Improved Fat Graft Retention by Promoting Adipogenesis and Angiogenesis

Background: Fat grafting is commonly used in treating soft-tissue defects. However, the basic biology behind fat grafting is still not fully understood. Evidence of adipose browning into beige adipose tissue after fat grafting was revealed, but its role in fat grafting remains unclear. Methods: Induced beige adipocytes and adipose-derived stem cells were obtained from human lipoaspirates and labeled with green fluorescent protein. Nude mice were each injected with 300 mg of human lipoaspirate containing green fluorescent protein-labeled adipose-derived stem cells, green fluorescent protein-labeled induced beige adipocytes, or phosphate-buffered saline. Grafted fat was harvested after 1, 4, 8, and 12 weeks for immunohistochemistry and histologic examination. Graft retention, vascularization, and adipogenic gene expression were compared. Results: After 7 days' induction, adipocytes achieved browning with multilocular lipid droplets, increased mitochondria, and up-regulated browning gene expression. Fat graft retention rates at week 12 were significantly higher after injection of induced beige adipocytes than after injection of phosphate-buffered saline (46.0 +/- 4.9 percent versus 31.0 +/- 3.6 percent; p = 0.01), but were similar after injection of induced beige adipocytes and adipose-derived stem cells (p > 0.05). Induced beige adipocytes underwent rewhitening into white adipocytes and showed up-regulation of peroxisome proliferator-activated receptor-. expression. Induced beige adipocytes enhanced angiogenesis, but were not active in forming vessel structures. Conclusions: Induced beige adipocytes and adipose-derived stem cells were comparable in improving fat graft retention rates. Induced beige adipocytes promote angiogenesis in a paracrine manner and are prone to rewhitening after fat grafting.