Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice

Leptin is a 16 kD protein that is produced by adipocytes and induces weight loss in both normal and genetically obese ob/ob mice, ob/ob mice are obese , have multiple metabolic abnormalities, and exhibit impaired wound healing . Exogenous administration of leptin to these animals induces weight loss a nd corrects their metabolic defects. Leptin's effect on wound repair, howev er, has not been studied. Systemic administration of leptin at doses rangin g from 0.1 to 10 mg/kg/day induced a highly significant acceleration in wou nd repair in ob/ob mice (p<0.0001), but not in db/db mice, indicating that leptin's effects on wound repair were mediated through the leptin receptor. We then investigated the possibility that leptin was acting directly at th e wound site by administering leptin topically, and found that topical lept in also induced a dose dependent acceleration in wound repair (p<0.0001). I n addition, we found that all forms of leptin receptor, including the signa l transducing long form, were present in skin by RNase protection assay, an d that leptin receptor localized to subcutaneous vessels of wounded skin by in situ hybridization. Finally, we investigated the possibility that lepti n stimulated angiogenesis in wounds by analyzing wound hemoglobin and wound vessel density. Neither systemic nor topical leptin induced any significan t changes in either parameter, suggesting that leptin accelerates wound rep air by a mechanism other than stimulation of angiogenesis. In summary, both systemic and topical leptin accelerate wound repair in diabetic ob/ob mice , possibly via the direct interaction of leptin with its receptors in wound ed skin, but do not appear to significantly stimulate wound angiogenesis. F urther studies to better elucidate the mechanisms of leptin's effects on wo und repair are warranted.