出版社:American Society for Biochemistry and Molecular Biology
摘要:Adiponutrin and a related protein, adipocyte triglyceride lipase(ATGL; also known as Desnutrin), were recently described asadipocyte-specific proteins with lipid hydrolase activity. Usingbioinformatics, we identified three additional Adiponutrin familymembers (GS2, GS2-Like, and PNPLA1). Here, we report on theexpression, regulation, and activity of GS2 and GS2-Like comparedwith Adiponutrin and Desnutrin/ATGL. GS2-Like is expressed andregulated in a manner similar to Adiponutrin; however, the absolutelevels of mRNA are significantly lower than those of Adiponutrinor Desnutrin/ATGL. GS2 transcripts were identified only in humansand are highly expressed in adipose as well as other tissues.All four proteins show lipase activity in vitro, which is dependenton the presence of the active site serine for Adiponutrin, Desnutrin/ATGL,and GS2. Overexpression of Desnutrin/ATGL, GS2, and GS2-Like,but not Adiponutrin, decreases intracellular triglyceride levels.This is consistent with a function for Desnutrin/ATGL, GS2,and GS2-Like in lipolysis, but not for Adiponutrin. Consistentwith previously reported data, Desnutrin/ATGL is upregulatedby fasting in adipose tissue, whereas Adiponutrin is downregulated.Additionally, Adiponutrin and GS2-Like, but not Desnutrin/ATGL,are strongly induced in the liver of ob/ob mice.
Our data support distinct functions for Adiponutrin and Desnutrin/ATGLand raise the possibility that GS2 may contribute significantlyto lipolysis in human adipose tissue.Abbreviations: ATGL, adipocyte triglyceride lipase; DGGR, 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester; EST, expressed sequence tag; HMM, hidden Markov model; HSL, hormone-sensitive lipase; OD, optical density; Q-PCR, quantitative reverse transcription polymerase chain reaction
Supplementary key words adipose tissue • adipocyte • lipolysis • Desnutrin • triglyceride lipase • patatin domain