Cold-Induced Browning: A Novel Method to Improve the Retention Rate of Fat Graft

Autologous fat grafting is frequently used to heal soft-tissue defects. The key restriction that must be addressed is the poor transplant retention rate. Growing evidence has demonstrated that the browning of white adipose tissue enhances the survival of fat grafts. We hypothesized that cold-induced browning before transplantation may be a novel method to improve fat graft survival.

Mice were kept in the 4 °C environment for 1 week, 2 weeks, and 3 weeks separately to detect whether different times of cold exposure could induce different numbers of beige adipocytes. Then, inguinal fat (roughly 150 mg) was collected and transferred. After post-graft weeks 4 and 12, the grafts were collected. The graft retention rate, histological morphology, vascularization, and browning were all assessed.

Mice inguinal fat showed enhanced beige adipose regeneration as the cold exposure (4 °C) time increased. Cold-induced browning resulted in greater retention, reduced fibrosis and necrosis, and improved angiogenesis at post-graft weeks 4 and 12. Simultaneously, few beige adipocytes were seen in grafts at post-graft weeks 4 and 12.

Cold-induced browning showed increased retention by promoting angiogenesis in a paracrine manner. Cold exposure of subcutaneous fat before transplantation may be a novel method to improve fat graft retention rate and retention quality.

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