There is increasing evidence of the interaction of fat and bone metabolism and the role mechanical signals may have in regulating the adaptation of these tissues. The rat hindlimb suspension model of disuse osteoporosis was used to identify genes differentially expressed relative to normal weight-bearing bones and whether the relative expression of these genes is sensitive to anabolic mechanical stimuli. Ten days of hindlimb suspension suppressed percent labeled surface and bone volume/trabecular volume of the proximal tibia by 46% and 69%, respectively, compared to controls. Differential display polymerase chain reaction (DD-PCR) and Northern blot analysis identified and verified, respectively, that expression of Spot 14 (S14), an important gene in lipogenesis, was upregulated fourfold in tibiae of tail-suspended animals compared to long-term controls. Anabolic mechanical stimulation (45 Hz, 10 min/day at 0.25 g) did not show a statistically significant effect on S14 expression. These results indicate a potential role for lipogenic genes during bone loss caused by disuse, further supporting a link between bone and fat tissue, and, considering the insensitivity of these genes to mechanical signals which promote bone formation in the skeleton, the independence of resorptive and formative processes in bone.