An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects.
An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects.
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DOI：
10.1210/en.2012-1277
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发表时间：
2012-06
期刊：
影响因子：
4.8
通讯作者：
M. van der Velde;B. V. D. van der Eerden;Yuxiang Sun;J. Almering;A. J. van der Lely;P. Delhanty;Roy G. Smith;J. V. van Leeuwen
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文献类型：
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作者：
M. van der Velde;B. V. D. van der Eerden;Yuxiang Sun;J. Almering;A. J. van der Lely;P. Delhanty;Roy G. Smith;J. V. van Leeuwen
能量稳态和骨代谢之间的相互作用是一个重要的新兴概念。Ghrelin和瘦素在调节能量平衡中相互拮抗，但这种相互作用在骨代谢中的作用尚不清楚。使用生长素释放肽受体和瘦素缺陷小鼠，我们表明，生长素释放肽对破骨细胞生成具有双重作用，直接抑制破骨细胞祖细胞，并通过更有效的系统/中枢途径刺激破骨细胞生成。使用结合生长激素释放肽受体和瘦素缺乏症的小鼠，我们发现这种系统性破骨细胞生成活性被瘦素抑制，从而平衡了两个反调节生长激素释放肽途径，并导致骨结构不变。随着年龄的增长，这种破骨细胞生成的ghrelin途径丢失，揭示了ghrelin对骨结构的直接保护作用。总之，我们确定了一个新的调节网络连接食欲和厌食代谢因子与骨代谢是年龄依赖性的。
The mutual interplay between energy homeostasis and bone metabolism is an important emerging concept. Ghrelin and leptin antagonize each other in regulating energy balance, but the role of this interaction in bone metabolism is unknown. Using ghrelin receptor and leptin-deficient mice, we show that ghrelin has dual effects on osteoclastogenesis, inhibiting osteoclast progenitors directly and stimulating osteoclastogenesis via a more potent systemic/central pathway. Using mice with combined ghrelin receptor and leptin deficiency, we find that this systemic osteoclastogenic activity is suppressed by leptin, thus balancing the two counterregulatory ghrelin pathways and leading to an unchanged bone structure. With aging, this osteoclastogenic ghrelin pathway is lost, unmasking the direct protective effect of ghrelin on bone structure. In conclusion, we identify a novel regulatory network linking orexigenic and anorectic metabolic factors with bone metabolism that is age dependent.