title: Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice.
abstract: 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.
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gelling
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yan
authors.forename: Salwa
authors.initials: S
authors.lastname: Al-Noori
authors.forename: Aaron
authors.initials: A
authors.lastname: Pardini
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dempsey
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency* / Q000235:genetics; D000072198:ADAM17 Protein; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005223:Fats / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D010641:Phenotype; D013851:Thinness / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D000071256:Uncoupling Protein 1
chemical_list: D005223:Fats; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse