Swimming exercise counteracts metabolic and skeletal dysfunction in LDL receptor-deficient mice exposed to a high-fat diet

PURPOSE: Swimming exercise is widely recognized as an effective non-pharmacological intervention for the management of metabolic disorders; however, its impact on the interplay between dyslipidemia and skeletal integrity remains incompletely understood. This study investigated whether swimming exercise attenuates metabolic and bone alterations in low-density lipoprotein receptor-deficient (LDLr⁻/⁻) mice exposed to a high-fat diet (HFD). METHODS: Mice were assigned to sedentary or exercise-trained groups and fed either standard chow or HFD. The training protocol consisted of daily swimming sessions (40 min/day) for 60 days. RESULTS: LDLr⁻/⁻ mice displayed a marked hyperlipidemic phenotype, which was significantly attenuated by exercise, as evidenced by reduced total cholesterol and triglyceride concentrations and increased high-density lipoprotein levels. In parallel, exercise restored plasma calcium levels, suggesting improved mineral homeostasis. Sedentary LDLr⁻/⁻ mice exposed to HFD exhibited pronounced impairments in cortical and trabecular bone compartments, accompanied by reduced calcium levels and adverse lipid profiles. In contrast, exercise-trained animals, irrespective of genotype or diet, showed preservation of bone structural and mechanical properties. These findings indicate that swimming exercise mitigates both metabolic and skeletal dysfunction associated with LDL receptor deficiency and HFD exposure. CONCLUSION: The results support a role for aerobic exercise in maintaining systemic homeostasis under dyslipidemic conditions and highlight its potential as a non-pharmacological strategy to prevent the deleterious effects of combined genetic and dietary risk factors.