Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice.
Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice.
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DOI：
10.1530/joe-15-0473
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发表时间：
2016-06
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影响因子：
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通讯作者：
Bouxsein ML
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文献类型：
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作者：
Devlin MJ;Brooks DJ;Conlon C;Vliet Mv;Louis L;Rosen CJ;Bouxsein ML
饥饿诱导人类低骨量和高骨髓脂肪，但其潜在机制尚不清楚。脂肪因子瘦素在饥饿时下降，提示低瘦素血症可能是负能量平衡、骨髓脂肪积累和骨骼获得受损之间的联系。如果是这样，在热量限制（CR）期间用瘦素治疗小鼠应该减少骨髓脂肪组织（MAT）并改善骨量。为了验证这一假设，雌性C57Bl/6J小鼠从5-10周龄开始饲喂30%卡路里限制（CR）或正常(N)饮食，每天注射药体（VEH）、1 mg/kg瘦素（LEP1）或2 mg/kg瘦素（LEP2） （N= 6-8 /组）。结果包括体质量、体脂率、全身骨密度（BMD） （pDXA）、皮质微结构和骨小梁微结构（μCT）、四氧化锇染色骨MAT体积（μCT）。总体而言，CR小鼠的体质量、体脂率、骨密度和皮质骨面积分数较低，但连接小梁较多（p<0.05）。最重要的是，虽然CR小鼠的MAT总体上高于N，但瘦素治疗使CR小鼠的MAT形成比对照减少了50%（两种瘦素剂量均p<0.05）。在9-10周龄时，CR LEP2小鼠比CR VEH小鼠体重更轻（p<0.05），但瘦素治疗对两种饮食中%体脂、骨密度或骨微结构均无影响。这些数据表明，在CR期间每天服用一次瘦素可抑制骨髓脂肪扩张而不影响骨量获取，这表明瘦素对饥饿诱导的骨髓脂肪形成和骨骼获取有明显的影响。
Starvation induces low bone mass and high bone marrow adiposity in humans, but the underlying mechanisms are poorly understood. The adipokine leptin falls in starvation, suggesting hypoleptinemia may be a link between negative energy balance, bone marrow fat accumulation and impaired skeletal acquisition. If so, treating mice with leptin during caloric restriction (CR) should reduce marrow adipose tissue (MAT) and improve bone mass. To test this hypothesis, female C57Bl/6J mice were fed a 30% calorie restricted (CR) or normal (N) diet from 5–10 weeks of age, with daily injections of vehicle (VEH), 1 mg/kg leptin (LEP1), or 2 mg/kg leptin (LEP2) (N=6–8/group). Outcomes included body mass, %body fat and whole body bone mineral density (BMD) via pDXA, cortical and trabecular microarchitecture via μCT, and MAT volume via μCT of osmium tetroxide-stained bones. Overall, CR mice had lower body mass, %body fat, BMD, and cortical bone area fraction, but more connected trabeculae, vs. N mice (p<0.05 for all). Most significantly, while MAT was elevated in CR vs. N overall, leptin treatment blunted MAT formation in CR mice by 50% vs. vehicle (p<0.05 for both leptin doses). CR LEP2 mice weighed less vs. CR VEH mice at 9–10 wks of age (p<0.05), but leptin treatment did not affect %body fat, BMD or bone microarchitecture within either diet. These data demonstrate that once daily leptin bolus during CR inhibits bone marrow adipose expansion without affecting bone mass acquisition, suggesting leptin has distinct effects on starvation-induced bone marrow fat formation and skeletal acquisition.