| First Author | Serino M | Year | 2007 |
| Journal | Diabetes | Volume | 56 |
| Issue | 10 | Pages | 2541-6 |
| PubMed ID | 17646208 | Mgi Jnum | J:126557 |
| Mgi Id | MGI:3761573 | Doi | 10.2337/db07-0360 |
| Citation | Serino M, et al. (2007) Mice heterozygous for tumor necrosis factor-alpha converting enzyme are protected from obesity-induced insulin resistance and diabetes. Diabetes 56(10):2541-6 |
| abstractText | OBJECTIVE: Tumor necrosis factor (TNF)-alpha is known to affect insulin sensitivity, glucose, and lipid metabolism through alternative and redundant mechanisms at both translational and post-translational levels. TNF-alpha exerts its paracrine effects once the membrane-anchored form is shed and released from the cell membrane. TNF-alpha cleavage is regulated by TNF-alpha converting enzyme (TACE), which regulates the function of several transmembrane proteins, such as interleukin-6 receptor and epidermal 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 protected from obesity and insulin resistance compared with wild-type littermates. When fed an HFD, wild-type mice exhibited visceral obesity, increased free fatty acid and monocyte chemoattractant protein (MCP)1 levels, hypoadiponectinemia, glucose intolerance, and insulin resistance compared with Tace(+/-) mice. Interestingly, Tace(+/-) mice exhibited increased uncoupling protein-1 and GLUT4 expression in white adipose tissue. CONCLUSIONS: Our results suggest that modulation of TACE activity is a new pathway to be investigated for development of agents acting against obesity and its metabolic complications. |
