High-fat diet and caffeine interact to modulate bone microstructure and biomechanics in mice

Aims: Although excessive fat and caffeine intake are independent risk factors for bone microstructural and functional disturbances, their association remains overlooked. Thus, we investigated the impact of high-fat diet (HFD) and caffeine alone and combined on serum lipid profile, bone microstructure, mi- cromineral distribution and biomechanical properties. Methods: Forty female C57BL/6 mice were randomized into 4 groups daily treated for seventeen weeks with standard diet (SD) or HFD (cafeteria diet) alone or combined with 50 mg/kg caffeine. Key findings: The association between HFD and caffeine reduced the weight gain compared to animals re- ceiving HFD alone. Caffeine alone or combined with HFD increases total and HDL cholesterol circulating levels. HFD also reduced calcium, phosphorus and magnesium bone levels compared to the groups receiv- ing SD, and this reduction was aggravated by caffeine coadministration. From biomechanical assays, HFD combined with caffeine increased bending strength and stiffness of tibia, a finding aligned with the marked microstructural remodeling of the cortical and cancellous bone in animals receiving this combina- tion. Significance: Our findings indicated that HFD and caffeine interact to induce metabolic changes and bone microstructural remodeling, which are potentially related to bone biomechanical adaptations in response to HFD and caffeine coadministration.