Early-life high-fat diet exposure increases Achilles tendon stiffness and induces transcriptomic alterations.

High-fat diet (HFD) exposure is a recognized risk factor for tendinopathy and impaired tendon healing in adults, yet its effects on baseline tendon properties following early-life exposure remain poorly understood. In this study, we investigated the structural, biomechanical, and transcriptomic characteristics of Achilles tendons in 12-week-old rat offspring born to dams fed an HFD or a normal diet during gestation. Compared with controls, HFD-exposed tendons exhibited a significant reduction in anteroposterior diameter on sagittal ultrasound imaging. However, histological assessment revealed comparable cellular density and collagen fiber organization between groups. Biomechanically, HFD exposure was associated with a significant increase in tendon stiffness, while the maximum tensile load was not significantly altered. Transcriptomic profiling identified 980 differentially expressed genes, including a marked downregulation of key tenogenic markers such as Scx and Eya2, along with an enrichment of pathways related to extracellular matrix remodeling and inflammation. Gene set enrichment further revealed an upregulation of inflammatory response, adipogenesis, and osteoblast differentiation signatures. Together, these findings demonstrate that early-life HFD exposure induces biomechanical and molecular alterations in intact Achilles tendons, suggesting compromised tendon quality that may increase susceptibility to mechanical overload and injury later in life.