Fat Grafting, Ischemia Repurfusion, Apoptosis, Antioxidants

Introduction: Lipoic acid (LA) is an organo-sulfur molecule and known component of aerobic cellular respiration that has strong antioxidant properties. In animal models it has been shown to modulate oxidative stress in ischemia reperfusion. We propose that fat-grafts undergo similar ischemic injury. Untreated fat grafts undergo apoptosis and cell-death during engraftment; leading ultimately to reabsorption. LA also has strong adipocyte specific signaling effects. LA has been shown to improve adipocyte mitochondrial function, insulin sensitivity, and glucose uptake. Thus, LA may modulate two significant pathways for cell death in adipocytes. We hypothesize that LA can reduce the oxidative stressors on fat grafts and improve mitochondrial function during the early engraftment period thereby improving long-term fat-graft survival. Methods: Human fat was obtained from liposuction aspirates, washed with saline, and centrifuged. The fat was then treated with either: LA; or saline control (NS). A nude mouse model was used for graft assessment; 1.0cc/1.0g lobules were implanted into bilateral flanks. Lobules were explanted and analyzed every third day for ten days, and then at six weeks. Samples were evaluated for apoptosis, weight, DNA content, and histology. Results: LA demonstrated, on average, the lowest levels of apoptosis compared to NS controls with peak improvements seen on day 6. NS demonstrated 35% reabsorption by weight at 6-weeks vs. 8% reabsorption in LA treated samples. LA treated samples also displayed 3-fold higher DNA content than NS treated controls. Histology of NS controls displayed large amounts of fibrosis; whereas, LA-treated fat appeared architecturally normal. Conclusions: LA is a potent anti-oxidant and immunomodulatory molecule with adipose specific effects relating to glucose transport and mitochondrial protection. We found that pretreatment of grafts with LA reduces early apoptosis in a nude mouse model during engraftment. At six-weeks we demonstrate significant improvements in weight, DNA content, and histology in LA treated grafts. LA alone or with other agents may be a new strategies for enhanced fat graft protection.