PDF(Pubmed)
Abstract：
Neurofibromatosis type 1 (NF1) is a complex genetic disorder that affects a range of tissues including muscle and bone. Recent preclinical and clinical studies have shown that Nf1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. These can be subsequently rescued by dietary interventions aimed at modulating lipid availability and metabolism. It was speculated that the modified diet may rescue defects in cortical bone as NF1 deficiency has been reported to affect genes involved with lipid metabolism. Bone specimens were analyzed from wild type control mice as well as Nf1Prx1-/- (limb-targeted Nf1 knockout mice) fed standard chow versus a range of modified chows hypothesized to influence lipid metabolism. Mice were fed from 4 weeks to 12 weeks of age. MicroCT analysis was performed on the cortical bone to examine standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae, and larger open pores). Nf1Prx1-/- bones were found to have inferior bone properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. These measures were rescued by dietary interventions including a L-carnitine + medium-chain fatty acid supplemented chow previously shown to improve muscle histology function. Histological staining visualized these changes in bone porosity. These data support the concept that lipid metabolism may have a mechanistic impact on bone porosity and quality in NF1.
摘要：
1型神经纤维瘤病（NF1）是一种复杂的遗传性疾病，影响包括肌肉和骨骼在内的一系列组织。最近的临床前和临床研究表明，肌肉中的Nf1缺乏会引起代谢变化，从而导致肌细胞内脂质积累和肌肉无力。这些可以随后通过旨在调节脂质可用性和代谢的饮食干预来挽救。据推测，改良饮食可能会挽救皮质骨的缺陷，因为据报道NF1缺乏会影响与脂质代谢有关的基因。分析了野生型对照小鼠以及饲喂标准食物的Nf1Prx1-/-（针对肢体的Nf1敲除小鼠）与一系列假定影响脂质代谢的改良食物的骨标本。从4周至12周龄饲喂小鼠。对皮质骨进行MicroCT分析以检查标准参数（骨体积，组织矿物质密度，皮质厚度）和特定的孔隙率措施（对应于骨细胞腔隙的闭孔，和较大的开放毛孔)。Nf1Prx1-/-骨被发现具有低于野生型骨的骨特性，孔隙度增加了4倍，这归因于开孔。这些措施是通过饮食干预措施来挽救的，这些饮食干预措施包括L-肉碱+补充中链脂肪酸的食物，这些食物先前显示可改善肌肉组织学功能。组织学染色显示了骨孔隙率的这些变化。这些数据支持以下概念：脂质代谢可能对NF1中的骨孔隙率和质量具有机械影响。
