Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase.
Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase.
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DOI：
10.3390/ijms18061264
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发表时间：
2017-06-13
影响因子：
5.6
通讯作者：
Niemeier A
中科院分区：
文献类型：
--
作者：
Bartelt A;Koehne T;Tödter K;Reimer R;Müller B;Behler-Janbeck F;Heeren J;Scheja L;Niemeier A
脂肪细胞是能量稳态的主要调节者。虽然经典棕色和白色脂肪组织（分别为BAT和WAT）对葡萄糖和脂肪酸代谢的贡献已得到很好的表征，但骨髓中脂肪细胞的代谢作用仍很不清楚。在这里，我们量化骨脂肪酸代谢及其对小鼠全身营养处理的贡献。虽然在骨骼的某些部分，从循环中吸收的营养物质的具体数量低于其他代谢活性组织，如BAT或肝脏，但骨骼作为一个整体器官的总体贡献是显着的，使其成为参与全身葡萄糖和脂肪酸清除的顶级器官之一。我们发现，在整个骨骼的骨髓脂肪酸组成有相当大的位点特异性变化，特别是在胫骨，骨髓脂肪酸谱类似于经典的BAT和WAT。使用缺乏脂蛋白脂酶（LPL），血浆脂质周转的主要调节剂，特别是在脂肪细胞的小鼠模型，我们表明，受损的脂肪酸流量导致减少量的膳食必需脂肪酸，而有一个深刻的增加从头产生的脂肪酸在骨髓和皮质骨。值得注意的是，脂肪酸谱的这些变化与任何大体骨骼表型无关。这些结果确定LPL作为脂肪酸转运到骨骼隔室的重要调节剂，并证明全身和骨骼脂肪酸和葡萄糖代谢之间存在复杂的功能联系。
Adipocytes are master regulators of energy homeostasis. Although the contributions of classical brown and white adipose tissue (BAT and WAT, respectively) to glucose and fatty acid metabolism are well characterized, the metabolic role of adipocytes in bone marrow remains largely unclear. Here, we quantify bone fatty acid metabolism and its contribution to systemic nutrient handling in mice. Whereas in parts of the skeleton the specific amount of nutrients taken-up from the circulation was lower than in other metabolically active tissues such as BAT or liver, the overall contribution of the skeleton as a whole organ was remarkable, placing it among the top organs involved in systemic glucose as well as fatty acid clearance. We show that there are considerable site-specific variations in bone marrow fatty acid composition throughout the skeleton and that, especially in the tibia, marrow fatty acid profiles resemble classical BAT and WAT. Using a mouse model lacking lipoprotein lipase (LPL), a master regulator of plasma lipid turnover specifically in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone. Notably, these changes in fatty acid profiles were not associated with any gross skeletal phenotype. These results identify LPL as an important regulator of fatty acid transport to skeletal compartments and demonstrate an intricate functional link between systemic and skeletal fatty acid and glucose metabolism.