Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice

Endocrinology. 2008 Dec;149(12):6053-64. doi: 10.1210/en.2008-0775. Epub 2008 Aug 7.


Energy homeostasis involves central nervous system integration of afferent inputs that coordinately regulate food intake and energy expenditure. Here, we report that adult homozygous TNFalpha converting enzyme (TACE)-deficient mice exhibit one of the most dramatic examples of hypermetabolism yet reported in a rodent system. Because this effect is not matched by increased food intake, mice lacking TACE exhibit a lean phenotype. In the hypothalamus of these mice, neurons in the arcuate nucleus exhibit intact responses to reduced fat mass and low circulating leptin levels, suggesting that defects in other components of the energy homeostasis system explain the phenotype of Tace(DeltaZn/DeltaZn) mice. Elevated levels of uncoupling protein-1 in brown adipose tissue from Tace(DeltaZn/DeltaZn) mice when compared with weight-matched controls suggest that deficient TACE activity is linked to increased sympathetic outflow. These findings collectively identify a novel and potentially important role for TACE in energy homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / deficiency*
  • ADAM Proteins / genetics
  • ADAM17 Protein
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Animals
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Blotting, Western
  • Cell Differentiation / physiology
  • Eating / physiology
  • Energy Metabolism / physiology*
  • Fats / metabolism
  • Hypothalamus / metabolism
  • Immunohistochemistry
  • Ion Channels / metabolism
  • Leptin / blood
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mitochondrial Proteins / metabolism
  • Motor Activity / physiology
  • Phenotype
  • Thinness / blood
  • Thinness / genetics
  • Thinness / physiopathology*
  • Uncoupling Protein 1


  • Fats
  • Ion Channels
  • Leptin
  • Mitochondrial Proteins
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • ADAM Proteins
  • ADAM17 Protein
  • Adam17 protein, mouse