Adipose Triglyceride Lipase-Null Mice Are Resistant to High-Fat Diet-Induced Insulin Resistance Despite Reduced Energy Expenditure and Ectopic Lipid Accumulation

Abstract

Adipose triglyceride lipase (ATGL) null (-/-) mice store vast amounts of triacylglycerol in key glucoregulatory tissues yet exhibit enhanced insulin sensitivity and glucose tolerance. The mechanisms underpinning these divergent observations are unknown but may relate to the reduced availability of circulating fatty acids. The aim of this study was to determine whether the enhancements in insulin stimulated glucose metabolism in ATGL-/- mice persist when challenged with a high-fat diet. ATGL-/- mice fed a low-fat diet exhibit improved whole-body insulin sensitivity and glucose tolerance compared with wild-type mice. Wild-type mice became hyperlipidemic and insulin-resistant when challenged wi..