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TNF-alpha Converting Enzyme heterozygous mice are protected from obesity-induced insulin resistance and diabetes

¹Laboratory of Molecular Medicine, Department of Internal Medicine,
²Department of Biopathology, University of Rome "Tor Vergata", Rome, Italy

Correspondence: federicm{at}uniroma2.it

Objective: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 transmembrane proteins, such as Interleukin-6 Receptor (IL-6R) and EGF Receptor ligands. The role of TACE in high fat diet 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 with a standard or high fat diet (HFD) for 16 weeks.

Results:We observed that Tace^+/– mice are relatively protected from obesity and insulin resistance compared with WT littermates. When fed a HFD, WT mice exhibited visceral obesity, increased FFA and Monocyte Chemoattractant Protein-1 (MCP1) levels, hypoadiponectinemia, glucose intolerance and insulin resistance compared with Tace^+/– mice. Interestingly, Tace^+/– mice exhibited increased UCP-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.

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