Previously we have shown that young mice with a dominant severe form of osteogenesis imperfecta (OI), caused by mutated collagen type I, exhibit an altered glucose/insulin metabolism and energy expenditure along with elevated levels of osteocalcin, a bone-derived hormone involved in the regulation of whole-body metabolism. This study aimed to examine the long-term effects of a western diet in these OI mice. Male and female OI mice and wild type littermates (WT) were fed a high-fat diet (HFD) or a matched low-fat diet (LFD) for 26 weeks. HFD-induced obesity was observed in male and female WT and female OI mice, but not in male OI mice. HFD-fed WT and OI mice of both sexes developed hyperglycemia and glucose intolerance, but the degree of glucose intolerance was significantly lower in male and female OI mice compared to sex- and diet-matched WT mice. Indirect calorimetry revealed increased movement of male OI mice on HFD compared to LFD and, while HFD lowered energy expenditure in WT mice, energy expenditure was not changed in OI mice. Further, HFD-fed male OI mice demonstrated a diet-induced increased expression of the thermogenesis genes, Ucp1 and Pgc1α, in brown adipose tissue. On LFD, total and Gla-13 osteocalcin levels were similar in 30-week-old WT and OI mice, but on HFD, both were significantly higher in OI mice than WT. Thus, male OI mice respond to HFD with increased movement, energy expenditure, brown adipose tissue thermogenesis, and higher levels of osteocalcin, resulting in partial protection against HFD-induced obesity.

以前我们已经证明，由突变的 I 型胶原蛋白引起的严重成骨不全症 (OI) 的年轻小鼠表现出葡萄糖/胰岛素代谢和能量消耗的改变以及骨钙素水平升高，骨钙素是一种骨源性激素，参与全身代谢的调节。本研究旨在检查西方饮食对这些 OI 小鼠的长期影响。雄性和雌性 OI 小鼠和野生型同窝仔 (WT) 被喂食高脂肪饮食 (HFD) 或匹配的低脂肪饮食 (LFD) 26 周。在雄性和雌性 WT 和雌性 OI 小鼠中观察到 HFD 诱导的肥胖，但在雄性 OI 小鼠中未观察到。HFD 喂养的两性 WT 和 OI 小鼠均出现高血糖和葡萄糖耐受不良，但与性别和饮食匹配的 WT 小鼠相比，雄性和雌性 OI 小鼠的葡萄糖耐受不良程度显着降低。间接量热法显示，与 LFD 相比，雄性 OI 小鼠在 HFD 上的运动增加，虽然 HFD 降低了 WT 小鼠的能量消耗，但 OI 小鼠的能量消耗没有改变。此外，HFD 喂养的雄性 OI 小鼠表现出饮食诱导的产热基因表达增加，Ucp1和Pgc1α，在棕色脂肪组织中。在 LFD 上，30 周龄 WT 和 OI 小鼠的总骨钙素和 Gla-13 骨钙素水平相似，但在 HFD 上，OI 小鼠的两者均显着高于 WT。因此，雄性 OI 小鼠对 HFD 的反应是增加运动、能量消耗、棕色脂肪组织产热和更高水平的骨钙素，从而部分保护免受 HFD 诱导的肥胖。