This influence was drastically reduced by the changes in the shape and distribution of the bars in the apparatus, which permitted to record the exact current passing precisely trough the paws of the animal during the task and to compare results among animals with different body composition.The mechanisms underlying these changes in ApoE tendons are not known at the present time. One possibility is that they result from the known susceptibility to inflammation of this mouse type. In line with this reasoning, PGE2 administration to tencoytes reduces collagen expression and increases MMP expression and activity – similar effects to those observed with exposure of tenocytes to oxLDL in this study. To further explore this possibility, future studies could attempt to use more sensitive methods to detect inflammatory substances in the tendons of ApoEmice, as we only detected scant histological evidence of inflammatory cells in the Achilles tendons of these animals. Following another line of reasoning, it has been previously observed that lipid droplets accumulate through direct interaction with the extracellular matrix in the aorta of ApoEmice. Therefore speculated to represent a primary mechanism by which atherosclerosis is initiated. Given the relative dearth of macrophages observed in the tendons of ApoEmice, the existence of a mechanism by which lipid accumulates directly in the tendon extracellular matrix may be even more revealing than an investigation of inflammatory pathways. Biomechanical testing of patellar tendons demonstrated a significant effect of high fat diet on tendon function. Torin 1 Previous literature on the biomechanical influences of diet and/or hypercholesterolemia is limited. Zhou et al examined the biomechanics of ApoEmice receiving a Western Diet, with or without one of four nutritional supplements; no differences were found in biomechanical properties among groups, however the data were not shown. Another study reported an increase in the tendon stiffness and modulus in the supraspinatus tendons of hypercholesterolemic mice compared to control mice, whereas a subsequent study by the same group reported a reduced modulus in the patellar tendons of aging ApoEmice compared to controls. Boivin et al studied the influence of high fat diet on C57Bl/6 female mice, and reported a reduced modulus and increased CSA of the Achilles tendon compared to standard diet. It is possible that the increased CSA observed in the study by Boivin et al resulted from the deposition of peritendinous fat, which was excluded from our US-based CSA measures. Despite the differences in methods between our study and Boivin’s, both are consistent in that high fat led to a loss of tendon biomechanical function.