Mice Heterozygous for Tumor Necrosis Factor- Converting Enzyme Are Protected From Obesity-Induced Insulin Resistance and Diabetes

OBJECTIVE—Tumor necrosis factor (TNF)- is known to affect insulin sensitivity, glucose, and lipid metabolism through alternative and redundant mechanisms at both translational and post-translational levels. TNF- exerts its paracrine effects once the membrane-anchored form is shed and released from the cell membrane. TNF- cleavage is regulated by TNF- converting enzyme (TACE), which regulates the function of several trans-membrane proteins, such as interleukin-6 receptor and epider-mal growth factor receptor ligands. The role of TACE in high-fat diet (HFD)-induced obesity and its metabolic complications is unknown. RESEARCH DESIGN AND METHODS—To gain insights into the role of TACE in metabolic disorders, we used Tace/ mice fed a standard or high-fat diet for 16 weeks. RESULTS—We observed that Tace/ mice are relatively pro