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EMBO reports 8, 12, 1183–1189 (2007)
doi:10.1038/sj.embor.7401086
AOP Published online: 12 October 2007
Tripeptidyl peptidase II promotes fat formation in a conserved fashion
Renée M McKay1*, James P McKay1*, Jae Myoung Suh1*, Leon Avery2 & Jonathan M Graff1, 2, 3
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1 Department of Developmental Biology
2 Department of Molecular Biology
3 Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas 75390-9113, USA
To whom correspondence should be addressed
Jonathan M Graff Tel: +1 214 648 1481; Fax: +1 214 648 1960; E-mail: jon.graff@utsouthwestern.edu
* These authors contributed equally to this work
Received 16 March 2007; Accepted 10 September 2007; Published online 12 October 2007.
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Abstract
Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner.
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