Decreased serum estrogen improves fat graft retention by enhancing early macrophage infiltration and inducing adipocyte hypertrophy

Background: Fat grafting is a commonly used procedure; however, the mechanisms that regulate graft outcomes are not clear. Estrogen has been associated with vascularization, inflammation and fat metabolism, yet its role in fat grafting is unclear. Methods: Mice were implanted with 17 beta-estradiol pellets (high estrogen, HE), underwent ovariectomy (low estrogen level, OVX) or sham surgery (normal estrogen level, CON). 45 days later, inguinal fat of mice was autografted subcutaneously. At 1, 2, 4, and 12 weeks post-transplantation, grafts were dissected, weighed, and assessed for histology, angiogenesis and inflammation level. Results: Serum estrogen level correlated to estrogen manipulation. 12 weeks after autografting, the retention rate was significantly higher in the OVX (79% +/- 30%) than in the HE (16% +/- 8%) and CON (35% +/- 13%) groups. OVX-grafts had the least necrosis and most hypertrophic fat. OVX recruited the most pro-inflammatory macrophages and demonstrated a faster dead tissue removal process, however a higher fibrogenic tendency was found in this group. HE grafts had the most Scal + local stem cells and CD31(+) capillary content; however, with a low level of acute inflammation and insufficient adipokine PPAR-gamma expression, their retention rate was impaired. Conclusions: Elevated serum estrogen increased stem cell density and early vascularization; however, by inhibiting the early inflammation, it resulted in delayed necrotic tissue removal and finally led to impaired adipose restoration. A low estrogen level induced favorable inflammation status and adipocyte hypertrophy to improve fat graft retention, but a continuing decreased estrogen level led to fat graft fibrosis. (C) 2018 Elsevier Inc. All rights reserved.