Low energy availability reduces bone mass and gonadal function in male mice
Low energy availability reduces bone mass and gonadal function in male mice
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DOI：
10.1007/s00774-023-01413-2
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发表时间：
2023-03-13
影响因子：
3.3
通讯作者：
Miyamoto, Takeshi
中科院分区：
文献类型：
--
作者：
Ito, Eri;Sato, Yuiko;Miyamoto, Takeshi
在女性中，以能量供应不足、功能性下丘脑闭经和骨质疏松为特征的女性运动员三联症是公认的应力性骨折的危险因素。应激损伤也发生在男性身上，但相比之下，其潜在的风险和机制还不太清楚。材料和方法5周大的野生型雄性小鼠被随意喂养(Ad)或接受60%的食物限制(FR)5周。在这两组小鼠中，一些小鼠被允许进入笼子里的锻炼轮，允许自愿跑轮(EX)和/或接受活性维生素D类似物治疗。结果雄性FR小鼠的睾丸重量、血清睾酮水平和骨量均显著降低。FR雄性小鼠的这种骨丢失通过运动而增加。组织学分析显示，FR或FR+运动(FR+EX)组小鼠的骨吸收和骨形成活性均显著降低，表现为骨转换低的状态。通过使用活性维生素D类似物治疗，FR或FR+EX雄性小鼠的骨量显著减少，成骨活性显著恢复。对骨重建起关键作用的胰岛素样生长因子I(IGF-I)水平在FR组显著低于对照组雄性小鼠。结论低能量供应也使男性处于应激性损伤的风险中，低能量供应是男性性腺功能障碍和骨质疏松的上游。活性维生素D类似物可以作为男性应激性损伤的治疗或预防选择。
IntroductionIn women, the female athlete triad, marked by low energy availability, functional hypothalamic amenorrhea and osteoporosis, is a recognized risk for stress fractures. Stress injuries also occur in men, but by contrast risks and mechanisms underlying them are less characterized.Materials and methods5 week-old wild-type male mice were fed ad libitum (ad) or subjected to 60% food restriction (FR) for five weeks. In both groups, some mice were allowed access to an exercise wheel in cages to allow voluntary wheel running (ex) and/or treated with active vitamin D analogues. Mice were sacrificed and analyzed at 10 weeks of age.ResultMale FR mice exhibited significantly reduced testicle weight, serum testosterone levels and bone mass. Such bone losses in FR male mice were enhanced by exercise. Histological analysis revealed that both bone-resorbing and -forming activities were significantly reduced in FR or FR plus exercise (FR + ex) mice, mimicking a state of low bone turnover. Significantly reduced bone mass in FR or FR + ex male mice was significantly rescued by treatment with active vitamin D analogues, with significant restoration of osteoblastic activities. Serum levels of insulin-like growth factor I (IGF-I), which is critical for bone remodeling, were significantly lower in FR versus control male mice.ConclusionsLow energy availability puts men at risk for stress injuries as well, and low energy availability is upstream of gonadal dysfunction and osteoporosis in males. Active vitamin D analogues could serve as therapeutic or preventive options for stress injuries in men.