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The role of Desnutrin/ATGL in promoting a brown‐adipose‐phenotype and regulation via AMPK
Author(s) -
Abbott Marcia J,
Ahmadian Maryam,
Sul Hei Sook
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb75
Subject(s) - adipose triglyceride lipase , adipose tissue , white adipose tissue , lipolysis , adipocyte , medicine , ampk , endocrinology , brown adipose tissue , chemistry , phosphorylation , phenotype , biology , protein kinase a , biochemistry , gene
Desnutrin/ATGL has been identified as the major triacylglycerol (TAG) lipase in adipose tissue and is induced during fasting. To further establish the role of desnutrin in adipocyte lipolysis we generated adipose‐specific knock‐out (ASKO) of desnutrin in mice. ASKO of desnutrin resulted in an obese phenotype with increased insulin sensitivity due to a decrease in circulating fatty acids (FA). The brown adipose tissue (BAT) in the desnutrin ASKO mice displayed a white adipose tissue (WAT)‐like phenotype with increased TAG, lower FA oxidation and less PPARα binding to its promoter. Desnutrin ASKO mice were cold intolerant and had lower expression of UCP‐1 in BAT. We also determined that the S406 residue of desnutrin is an important regulation site and is able to be phosphorylated by AMPK to increase its hydrolase activity. Immunoprecipitates from desnutrin overexpressed HEK 293 cells, treated with AICAR, had an increase in phosphorylation of desnutrin at S406. Mutation of S406 to alanine decreased lipase activity and increased TAG content in livers of adenovirus infected mice. These results suggest that desnutrin activity, in adipose tissue, may be regulated through AMPK to provide FA ligands for PPARα and promotes a BAT phenotype in WAT.