Leptin pretreatment of ob−/ob− osteoblasts abolished their enhanced mitogenic response to the fluid shear in vitro. Osteoblasts of ob−/ob− mice were pretreated for 2 h with or without 100 ng/ml leptin. Immediately after the pretreatment, these ob−/ob− osteoblasts along with B6 osteoblasts were subjected to the 30-min fluid shear stress of 20 dynes/cm2. [3H]Thymidine incorporation was determined as described (5). Results are shown as a percentage of corresponding static controls (mean ± S.D. (error bars), n = 6). *, p < 0.05, compared with static control; #, p < 0.05, compared with B6 osteoblasts.