Deletion of CD73 promotes dyslipidemia and intramyocellular lipid accumulation in muscle of mice
Deletion of CD73 promotes dyslipidemia and intramyocellular lipid accumulation in muscle of mice
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DOI：
10.3109/13813455.2012.755547
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发表时间：
2013-05-01
影响因子：
3
通讯作者：
Schrader, Juergen
中科院分区：
文献类型：
--
作者：
Burghoff, Sandra;Floegel, Ulrich;Schrader, Juergen
背景：CD 73将细胞外AMP转化为腺苷，腺苷被公认为抑制脂解。然而，目前尚不清楚由CD 73直接形成的腺苷在该过程中是否具有功能相关性。目的：探讨CD 73-腺苷对老年小鼠体脂的影响。结果：在瘦小鼠中，脂肪细胞的胞外腺苷形成依赖于CD 73。高脂饮食下调野生型小鼠中CD 73的表达，类似于ob/ob小鼠。长期缺乏CD 73（CD 73（-/-））的转基因小鼠体重增加显著减少，表面白色脂肪含量降低，血清游离脂肪酸和甘油三酯增加。此外，肌细胞内脂质水平显著增加。这种表型伴随着血糖和血清胰岛素水平的增加，尽管胰岛素分泌和胰岛素降解酶的水平没有改变。此外，胰岛素诱导的Akt磷酸化在CD 73（-/-）小鼠的骨骼肌中减少。结论：CD 73衍生的腺苷在功能上参与了体内脂肪稳态。
Context: CD73 converts extracellular AMP to adenosine which is well known to inhibit lipolysis. It is unknown, however, whether adenosine formed directly by CD73 is functionally relevant in this process. Objective: We therefore explored the effect of CD73-derived adenosine on body fat of aged mice. Results: In lean mice, extracellular adenosine formation by adipocytes is dependent on CD73. High fat diet down-regulates the expression of CD73 in wildtype mice similar to ob/ob mice. Transgenic mice chronically lacking CD73 (CD73(-/-)) gain significantly less body weight and show decreased superficial white fat content as well as increased serum free fatty acids and triglycerides. In addition, intramyocellular lipid levels are significantly increased. This phenotype is accompanied by an increase in blood glucose and serum insulin levels although insulin secretion and the level of insulin degrading enzyme are unaltered. Additionally, insulin-induced Akt phosphorylation is reduced in skeletal muscle of CD73(-/-) mice. Conclusion: CD73-derived adenosine is functionally involved in body fat homeostasis.