Defective Lipolysis and Altered Energy Metabolism in Mice Lacking Adipose Triglyceride Lipase

TLDR

Fat tissue is the primary energy depot in vertebrates, and lipases are required to release free fatty acids from stored fat. ATGL knockout mice exhibit increased adipose mass, triacylglycerol accumulation in multiple tissues—including the heart, where it causes dysfunction and premature death—impaired cold adaptation, and a metabolic shift toward greater glucose utilization, tolerance, and insulin sensitivity, underscoring ATGL’s rate‑limiting role in cellular fat catabolism and its importance for energy homeostasis.

Abstract

Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.