Systemic and organ specific metabolic variation in metallothionein knockout mice challenged with swimming exercise
- PDF / 672,115 Bytes
- 15 Pages / 595.276 x 790.866 pts Page_size
- 84 Downloads / 145 Views
ORIGINAL ARTICLE
Systemic and organ specific metabolic variation in metallothionein knockout mice challenged with swimming exercise Jeremie Zander Lindeque • Juan Hidalgo • Roan Louw • Francois Hendrikus van der Westhuizen
Received: 6 June 2012 / Accepted: 26 August 2012 / Published online: 5 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract 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
Electronic supplementary material The online version of this article (doi:10.1007/s11306-012-0459-8) contains supplementary material, which is available to authorized users. J. Z. Lindeque (&) R. Louw F. H. van der Westhuizen Centre for Human Metabonomics, North-West University, Potchefstroom Campus, Potchefstroom, South Africa e-mail: [email protected] J. Hidalgo Institute of Neurosciences, Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Autonomous University of Barcelona, Barcelona, Spain
123
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. Keywords Metabolomics Metallothioneins Mitochondria Energy production
1 Introduction Metallothioneins (MTs) are small, metal-binding proteins expressed in nearly all animal and plant species (Freisinger 2008). Their high cysteine content (*30 %) gives them the ability to bind 7–12 metals depending on the valence of the metals. These proteins are important in metal homeostasis (binding, transport and release of zinc and copper to enzymes and transcription factors), heavy metal detoxification (binding and excretion of heavy metals such as
Data Loading...
