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Papers In Press, published online ahead of print September 8, 2005
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Cardiovascular and Metabolic Diseases, Wyeth Research, Cambridge, MA 02140
Corresponding Author: rgimeno{at}wyeth.com
Adiponutrin and a related protein, Desnutrin/ATGL, 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 expression, regulation and activity of GS2 and GS2-Like in comparison 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 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, lowers 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, while 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.
Revised on August 12, 2005
Accepted on August 18, 2005
Expression, regulation and triglyceride hydrolase activity of adiponutrin family members
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