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Journal of Lipid Research, Vol. 46, 2477-2487, November 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members
* Biological Technologies, Wyeth Research, Cambridge, MA 02140
Cardiovascular and Metabolic Diseases, Wyeth Research, Cambridge, MA 02140
Published, JLR Papers in Press, September 8, 2005. DOI 10.1194/jlr.M500290-JLR200
1 To whom correspondence should be addressed. e-mail: rgimeno{at}wyeth.com
Adiponutrin and a related protein, adipocyte triglyceride lipase (ATGL; also known as Desnutrin), were recently described as adipocyte-specific proteins with lipid hydrolase activity. Using bioinformatics, we identified three additional Adiponutrin family members (GS2, GS2-Like, and PNPLA1). Here, we report on the expression, regulation, and activity of GS2 and GS2-Like compared with Adiponutrin and Desnutrin/ATGL. GS2-Like is expressed and regulated in a manner similar to Adiponutrin; however, the absolute levels of mRNA are significantly lower than those of Adiponutrin or Desnutrin/ATGL. GS2 transcripts were identified only in humans and are highly expressed in adipose as well as other tissues. All four proteins show lipase activity in vitro, which is dependent on 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. Consistent with previously reported data, Desnutrin/ATGL is upregulated by 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/ATGL and raise the possibility that GS2 may contribute significantly to 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
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