Strain differences in the attenuation of bone accrual in a young growing mouse model of insulin resistance

摘要: Skeletal fractures are considered a chronic complication of type 2 diabetes mellitus (T2DM), but the etiology compromised bone quality that develops over time remains uncertain. This study investigated concurrent alterations in metabolic and skeletal changes two mouse strains, responsive (C57BL/6) relatively resistant (C3H/HeJ) strain, to high-fat diet-induced glucose intolerance. Four-week-old male C57BL/6 C3H/HeJ mice were randomized control (Con = 10 % kcal fat) or (HF = 60 % diet for 2, 8, 16 weeks. Metabolic changes, including blood glucose, plasma insulin leptin, tolerance monitored conjunction with structure turn over. Elevated fasting occurred both strains on HF at 8 weeks, only strain Both demonstrated impaired each point. The exhibited lower whole-body mineral density (BMD) by 8 16 weeks, had no evidence loss until Analyses microarchitecture revealed trabecular accrual distal femur metaphysis was attenuated In contrast, protected from deleterious effects bone. Alterations gene expression several toll-like receptor (TLR)-4 targets (Atf4, Socs3, Tlr4) regulated not strain. Structural observed accompanied decrease osteoblastogenesis after 16 weeks diet, suggesting TLR-4-mediated mechanism suppression formation. an increase osteoclastogenesis 8 weeks diet; however, turnover decreased prolonged hyperglycemia. Further investigation is needed understand how hyperglycemia hyperinsulinemia suppress context T2DM role TLR-4 this response.