Deletion of CD73 promotes dyslipidemia and intramyocellular lipid accumulation in muscle of mice

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.