The role of adipose triglyceride lipase in lipid and glucose homeostasis: lessons from transgenic mice

The ability of mammals to store and draw on fat reserves has been a driving force throughout evolution in an environment with intermittent nutrient availability. The discovery of adipose triglyceride lipase (ATGL) as a triglyceride lipase provided a heightened understanding of the mechanisms governing mobilization of fat reserves from adipose tissue. ATGL catalyses the initial step in adipose triglyceride lipolysis, working in concert with other enzymes to mobilize triglyceride for energy production. In addition to the role of ATGL in adipose tissue triglyceride mobilization, ATGL plays crucial roles in regulating lipid homeostasis in other tissues. These roles have been characterized primarily using transgenic mice with tissue-specific ATGL ablation. For example, the global ATGL knockout induces a severe cardiac defect that results in premature mortality that is mimicked by inducible cardiomyocyte-specific ATGL knockout. Global- and adipose-specific ATGL ablation induces a whole-body shift from lipid metabolism to glucose metabolism to satisfy metabolic demand primarily facilitated by an increase in glucose uptake by skeletal muscle. Generation of liver-specific ATGL knockouts has implicated hepatic lipolysis as a critical component of normal liver function. Analysis of β-cell ATGL knockouts implicates the necessity of pancreatic ATGL in insulin secretion. The objective of this review is to discuss the contributions of ATGL to systemic lipid- and glucose-homeostasis discovered through the study of transgenic mice.