Systemic and organ specific metabolic variation in metallothionein knockout mice challenged with swimming exercise
Date
2013Author
Lindeque, Jeremie Zander
Louw, Roan
Van der Westhuizen, Francois Hendrikus
Hidalgo, Juan
Metadata
Show full item recordAbstract
Metallothioneins (MTs) are ubiquitous, multifunctional
proteins with key roles in metal homeostasis and
redox regulation. Their involvement in cellular energy
metabolism is evident from the observation that metallothionein-
knockout (MTKO) mice become moderately obese.
Transcriptomic studies have also indicated that several genes
associated with energy metabolism are differentially expressed
in these mice. Although single varying metabolites have
been reported, the roles of MTs on a global metabolic level
have not been investigated before. In this study, an untargeted,
hypothesis-generating metabolomics approach was
used to identify and report all metabolites that differ in relative
concentration between MT1?2KO, MT3KO and wildtype
(WT) mice before and after an exercise (1 h swim)
perturbation. PCA and univariate results confirmed that the
metabolism of the MTKO mice differs from the WT during
unchallenged conditions and hypothetically pointed to
increased anabolic activity which could contribute to their
previously reported tendency to become obese. Furthermore,
the metabolic differences observed in the liver after the 1 h
swim indicated that catabolic activity might be impaired in
these mice, which could be a consequence of a dysfunction of
a common catabolic signal. The MT3KO mice did not show
the same metabolic pattern as the MT1?2KO mice as most
metabolite concentrations in the brain of these mice were
lower after the 1 h swim. The reported metabolic variation
contributes to better understand the diverse functionality of
these ubiquitous proteins on a global phenotypic level.
URI
http://hdl.handle.net/10394/14686https://doi.org/10.1007/s11306-012-0459-8
https://link.springer.com/article/10.1007/s11306-012-0459-8