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SLEEP AND TEMPERATURE REGULATION

Metabolomic profiling of heat stress: hardening and recovery of homeostasis in Drosophila

¹Center for Insoluble Protein Structures, Interdisciplinary Nanoscience Center, and Department of Chemistry, University of Aarhus, Aarhus, Denmark; ²National Environmental Research Institute, Department of Terrestrial Ecology, Silkeborg, Denmark; ³Aarhus Centre for Environmental Stress Research, Department of Genetics and Ecology, Institute of Biological Sciences, University of Aarhus, Aarhus, Denmark; and ⁴Biomedical Sciences Division (Biological Chemistry Section), Imperial College, London, United Kingdom

Submitted 9 December 2005 ; accepted in final form 6 February 2006

Frequent exposure of terrestrial insects to temperature variation has led to the evolution of protective biochemical and physiological mechanisms, such as the heat shock response, which markedly increases the tolerance to heat stress. Insight into such mechanisms has, so far, mainly relied on selective studies of specific compounds or characteristics or studies at the genomic or proteomic levels. In the present study, we have used untargeted NMR metabolomic profiling to examine the biological response to heat stress in Drosophila melanogaster. The metabolite profile was analyzed during recovery after exposure to different thermal stress treatments and compared with untreated controls. Both moderate and severe heat stress gave clear effects on the metabolite profiles. The profiles clearly demonstrated that hardening by moderate heat stress led to a faster reestablishment of metabolite homeostasis after subsequent heat stress. Several metabolites were identified as responsive to heat stress and could be related to known physiological and biochemical responses. The time course of the recovery of metabolite homeostasis mirrored general changes in gene expression, showing that recovery follows the same temporal pattern at these two biological levels. Finally, our data show that heat hardening permits a quicker return to homeostasis, rather than a reduction of the acute metabolic perturbation and that the reestablishment of homeostasis is important for obtaining maximal heat-hardening effect. The results display the power of NMR metabolomic profiling for characterization of the instantaneous physiological condition, enabling direct visualization of the perturbation of and return to homeostasis.

metabolomics; heat shock protein; nuclear magnetic resonance spectroscopy; insect

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