Function, Regulation by Insulin, and Comparison With Adiponutrin

Adipose triglyceride lipase (ATGL) is a recently described adipose-enriched protein with triglyceride-specific lipase activity. ATGL shares the greatest sequence homology with adiponutrin, a nutritionally regulated protein of unclear biological function. Here we present a functional analysis of ATGL and adiponutrin and describe their regulation by insulin. Retroviral-mediated overexpression of ATGL in 3T3-L1 adipocytes increased basal and isoproterenol-stim-ulated glycerol and nonesterified fatty acid (NEFA) re-lease, whereas siRNA-mediated knockdown of ATGL had the opposite effect. In contrast, siRNA-mediated knock-down of adiponutrin in 3T3-L1 adipocytes had no effect on glycerol or NEFA release. In mice, both ATGL and adipo-nutrin are nutritionally regulated in adipose tissue, with ATGL being upregulated and adiponutrin being downregu