Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner
Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner
复制标题
DOI：
10.1172/jci.insight.92704
复制
发表时间：
2017-08-17
期刊：
影响因子：
8
通讯作者：
Riddle, Ryan C.
中科院分区：
文献类型：
--
作者：
Kim, Soohyun P.;Li, Zhu;Riddle, Ryan C.
出生后的骨形成受营养状况的影响，并受到代谢紊乱的影响。膳食脂质的氧化代表了许多细胞ATP的重要来源，但在骨骼中的研究很少，其中流行的观点是葡萄糖是主要的能量来源。在这里，我们研究了脂肪酸的吸收骨和探测的要求脂肪酸catalysts在骨形成过程中，具体破坏肉毒碱棕榈酰转移酶2（Cpt2），一种专性酶的脂肪酸氧化，在成骨细胞和骨细胞的表达。放射性示踪剂研究表明，骨骼积累了相当一部分的餐后脂肪酸，这是等于或超过骨骼肌或脂肪组织收购。女性，但不是男性，Cpt2突变小鼠表现出显着的损伤，在出生后的骨收购，可能是由于成骨细胞无法修改燃料选择。有趣的是，成骨细胞和骨细胞对脂肪酸利用的抑制也导致了血脂异常和身体组成的饮食依赖性改变。总之，这些研究表明，在骨积累过程中需要脂肪酸氧化，并表明骨骼在脂质稳态中的作用。
Postnatal bone formation is influenced by nutritional status and compromised by disturbances in metabolism. The oxidation of dietary lipids represents a critical source of ATP for many cells but has been poorly studied in the skeleton, where the prevailing view is that glucose is the primary energy source. Here, we examined fatty acid uptake by bone and probed the requirement for fatty acid catabolism during bone formation by specifically disrupting the expression of carnitine palmitoyltransferase 2 (Cpt2), an obligate enzyme in fatty acid oxidation, in osteoblasts and osteocytes. Radiotracer studies demonstrated that the skeleton accumulates a significant fraction of postprandial fatty acids, which was equal to or in excess of that acquired by skeletal muscle or adipose tissue. Female, but not male, Cpt2 mutant mice exhibited significant impairments in postnatal bone acquisition, potentially due to an inability of osteoblasts to modify fuel selection. Intriguingly, suppression of fatty acid utilization by osteoblasts and osteocytes also resulted in the development of dyslipidemia and diet-dependent modifications in body composition. Taken together, these studies demonstrate a requirement for fatty acid oxidation during bone accrual and suggest a role for the skeleton in lipid homeostasis.