Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Plastic and Cosmetic Surgery, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China.
FASEB J. 2024 Mar 15;38(5):e23520. doi: 10.1096/fj.202302090R.
Fat grafting is a promising technique for correcting soft tissue abnormalities, but oil cyst formation and graft fibrosis frequently impede the therapeutic benefit of fat grafting. The lipolysis of released oil droplets after grafting may make the inflammation and fibrosis in the grafts worse; therefore, by regulating adipose triglyceride lipase (ATGL) via Atglistatin (ATG) and Forskolin (FSK), we investigated the impact of lipolysis on fat grafts in this study. After being removed from the mice and chopped into small pieces, the subcutaneous fat from wild-type C57BL/6J mice was placed in three different solutions for two hours: serum-free cell culture medium, culture medium+FSK (50 μM), and culture medium+ATG (100 μM). Following centrifugation to remove water and free oil droplets, 0.3 mL of the fat particles per mouse was subcutaneously injected into the back of mice. Additionally, the subcutaneous fat grafting area was immediately injected with PBS (control group), ATG (30 mg/kg), and FSK (15 mg/kg) following fat transplantation. Detailed cellular events after grafting were investigated by histological staining, real-time polymerase chain reaction, immunohistochemistry/immunofluorescent staining, and quantification. Two weeks after grafting, grafts treated with ATG showed lower expression of ATGL and decreased mRNA levels of TNFα and IL-6. In contrast, grafts treated with ATG showed elevated expression levels of IL-4 and IL-13 compared to the control grafts. In addition, fewer apoptotic cells and oil cysts were observed in ATG grafts. Meanwhile, a higher CD206+/CD68+ ratio of macrophages and more CD31+ vascular endothelial cells existed in the 2-month ATG grafts. In comparison to the control, ATG treatment improved the volume retention of grafts, and decreased graft fibrosis and oil cyst formation. By preventing oil droplet lipolysis, pharmacological suppression of ATGL shielded adipocytes from lipotoxicity following grafting. Additionally, ATG ameliorated the apoptosis and inflammation brought on by adipocyte death and oil droplet lipolysis in grafted fat. These all indicate that lipolysis inhibition improved transplanted fat survival and decreased the development of oil cysts and graft fibrosis, offering a potential postoperative pharmacological intervention for bettering fat grafting.
脂肪移植是一种有前途的技术，可用于矫正软组织异常，但油囊肿形成和移植物纤维化常阻碍脂肪移植的治疗效果。移植后释放的油滴的脂解作用可能使移植物中的炎症和纤维化加重；因此，通过用 Atglistatin（ATG）和 Forskolin（FSK）调节脂肪甘油三酯脂肪酶（ATGL），我们研究了脂解作用对脂肪移植的影响。从小鼠体内取出并切成小块的皮下脂肪，放置在三种不同的溶液中两小时：无血清细胞培养液、培养液+FSK（50μM）和培养液+ATG（100μM）。离心去除水分和游离油滴后，将每只小鼠 0.3ml 的脂肪颗粒皮下注射到小鼠背部。此外，在脂肪移植后，立即向皮下脂肪移植区域注射 PBS（对照组）、ATG（30mg/kg）和 FSK（15mg/kg）。通过组织学染色、实时聚合酶链反应、免疫组织化学/免疫荧光染色和定量分析研究移植后的详细细胞事件。移植后两周，用 ATG 处理的移植物中 ATGL 的表达降低，TNFα 和 IL-6 的 mRNA 水平降低。相反，与对照组移植物相比，用 ATG 处理的移植物中 IL-4 和 IL-13 的表达水平升高。此外，在 ATG 移植物中观察到更少的凋亡细胞和油囊肿。同时，在 2 个月的 ATG 移植物中，巨噬细胞的 CD206+/CD68+比值更高，CD31+血管内皮细胞更多。与对照组相比，ATG 治疗改善了移植物的体积保留，并减少了移植物纤维化和油囊肿形成。通过防止油滴脂解，药理学抑制 ATGL 可防止移植后脂肪细胞发生脂毒性。此外，ATG 改善了脂肪细胞死亡和油滴脂解引起的移植物中的细胞凋亡和炎症。所有这些都表明，脂解抑制改善了移植脂肪的存活率，并减少了油囊肿和移植物纤维化的发展，为改善脂肪移植提供了一种潜在的术后药理学干预措施。
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