PDF(Pubmed)
Abstract：
UNASSIGNED: Caloric restriction (CR) is a nutritional intervention that increases life expectancy while lowering the risk for cardio-metabolic disease. Its effects on bone health, however, remain controversial. For instance, CR has been linked to increased accumulation of bone marrow adipose tissue (BMAT) in long bones, a process thought to elicit detrimental effects on bone. Qualitative differences have been reported in BMAT in relation to its specific anatomical localization, subdividing it into physiological and potentially pathological BMAT. We here examine the local impact of CR on bone composition, microstructure and its endocrine profile in the context of aging.
UNASSIGNED: Young and aged male C57Bl6J mice were subjected to CR for 8 weeks and were compared to age-matched littermates with free food access. We assessed bone microstructure and BMAT by micro-CT, bone fatty acid and transcriptomic profiles, and bone healing.
UNASSIGNED: CR increased tibial BMAT accumulation and adipogenic gene expression. CR also resulted in elevated fatty acid desaturation in the proximal and mid-shaft regions of the tibia, thus more closely resembling the biochemical lipid profile of the distally located, physiological BMAT. In aged mice, CR attenuated trabecular bone loss, suggesting that CR may revert some aspects of age-related bone dysfunction. Cortical bone, however, was decreased in young mice on CR and remained reduced in aged mice, irrespective of dietary intervention. No negative effects of CR on bone regeneration were evident in either young or aged mice.
UNASSIGNED: Our findings indicate that the timing of CR is critical and may exert detrimental effects on bone biology if administered during a phase of active skeletal growth. Conversely, CR exerts positive effects on trabecular bone structure in the context of aging, which occurs despite substantial accumulation of BMAT. These data suggest that the endocrine profile of BMAT, rather than its fatty acid composition, contributes to healthy bone maintenance in aged mice.
UNASSIGNED: Young and aged male C57Bl6J mice were subjected to CR for 8 weeks and were compared to age-matched littermates with free food access. We assessed bone microstructure and BMAT by micro-CT, bone fatty acid and transcriptomic profiles, and bone healing.
UNASSIGNED: CR increased tibial BMAT accumulation and adipogenic gene expression. CR also resulted in elevated fatty acid desaturation in the proximal and mid-shaft regions of the tibia, thus more closely resembling the biochemical lipid profile of the distally located, physiological BMAT. In aged mice, CR attenuated trabecular bone loss, suggesting that CR may revert some aspects of age-related bone dysfunction. Cortical bone, however, was decreased in young mice on CR and remained reduced in aged mice, irrespective of dietary intervention. No negative effects of CR on bone regeneration were evident in either young or aged mice.
UNASSIGNED: Our findings indicate that the timing of CR is critical and may exert detrimental effects on bone biology if administered during a phase of active skeletal growth. Conversely, CR exerts positive effects on trabecular bone structure in the context of aging, which occurs despite substantial accumulation of BMAT. These data suggest that the endocrine profile of BMAT, rather than its fatty acid composition, contributes to healthy bone maintenance in aged mice.
摘要：
■热量限制（CR）是一种营养干预措施，可增加预期寿命，同时降低心脏代谢疾病的风险。它对骨骼健康的影响，然而,仍然有争议。例如,CR与长骨中骨髓脂肪组织（BMAT）的积累增加有关，一个被认为对骨骼产生有害影响的过程。据报道，BMAT在其特定解剖定位方面存在定性差异，将其细分为生理性和潜在病理性BMAT。我们在这里检查CR对骨成分的局部影响，衰老背景下的微观结构及其内分泌特征。
■年轻和年老的雄性C57Bl6J小鼠接受CR8周，并与年龄匹配的同窝动物进行比较，免费获得食物。我们通过显微CT评估骨微结构和BMAT，骨脂肪酸和转录组概况，骨愈合。
■CR增加了胫骨BMAT的积累和成脂基因的表达。CR还导致胫骨近端和中轴区域的脂肪酸去饱和升高，因此更接近于远端位置的生化脂质分布，生理BMAT。在老年小鼠中，CR减弱小梁骨丢失，提示CR可能逆转年龄相关性骨功能障碍的某些方面。皮质骨,然而,在CR的年轻小鼠中降低，在老年小鼠中保持降低，不考虑饮食干预。在年轻或老年小鼠中，CR对骨再生的负面影响均不明显。
■我们的发现表明，CR的时机至关重要，如果在活跃的骨骼生长阶段施用，可能会对骨骼生物学产生不利影响。相反，在衰老的背景下，CR对小梁骨结构产生积极影响，尽管BMAT大量积累，但仍发生这种情况。这些数据表明，BMAT的内分泌特征，而不是它的脂肪酸组成，有助于老年小鼠的健康骨骼维护。
■年轻和年老的雄性C57Bl6J小鼠接受CR8周，并与年龄匹配的同窝动物进行比较，免费获得食物。我们通过显微CT评估骨微结构和BMAT，骨脂肪酸和转录组概况，骨愈合。
■CR增加了胫骨BMAT的积累和成脂基因的表达。CR还导致胫骨近端和中轴区域的脂肪酸去饱和升高，因此更接近于远端位置的生化脂质分布，生理BMAT。在老年小鼠中，CR减弱小梁骨丢失，提示CR可能逆转年龄相关性骨功能障碍的某些方面。皮质骨,然而,在CR的年轻小鼠中降低，在老年小鼠中保持降低，不考虑饮食干预。在年轻或老年小鼠中，CR对骨再生的负面影响均不明显。
■我们的发现表明，CR的时机至关重要，如果在活跃的骨骼生长阶段施用，可能会对骨骼生物学产生不利影响。相反，在衰老的背景下，CR对小梁骨结构产生积极影响，尽管BMAT大量积累，但仍发生这种情况。这些数据表明，BMAT的内分泌特征，而不是它的脂肪酸组成，有助于老年小鼠的健康骨骼维护。
