, Volume 185, Issue 2, pp 195–203 | Cite as

Chronic stress, energy transduction, and free-radical production in a reptile

  • Yann Voituron
  • Rémy Josserand
  • Jean-François Le Galliard
  • Claudy Haussy
  • Damien Roussel
  • Caroline Romestaing
  • Sandrine Meylan
Physiological ecology - original research


Stress hormones, such as corticosterone, play a crucial role in orchestrating physiological reaction patterns shaping adapted responses to stressful environments. Concepts aiming at predicting individual and population responses to environmental stress typically consider that stress hormones and their effects on metabolic rate provide appropriate proxies for the energy budget. However, uncoupling between the biochemical processes of respiration, ATP production, and free-radical production in mitochondria may play a fundamental role in the stress response and associated life histories. In this study, we aim at dissecting sub-cellular mechanisms that link these three processes by investigating both whole-organism metabolism, liver mitochondrial oxidative phosphorylation processes (O2 consumption and ATP production) and ROS emission in Zootoca vivipara individuals exposed 21 days to corticosterone relative to a placebo. Corticosterone enhancement had no effect on mitochondrial activity and efficiency. In parallel, the corticosterone treatment increased liver mass and mitochondrial protein content suggesting a higher liver ATP production. We also found a negative correlation between mitochondrial ROS emission and plasma corticosterone level. These results provide a proximal explanation for enhanced survival after chronic exposure to corticosterone in this species. Importantly, none of these modifications affected resting whole-body metabolic rate. Oxygen consumption, ATP, and ROS emission were thus independently affected in responses to corticosterone increase suggesting that concepts and models aiming at linking environmental stress and individual responses may misestimate energy allocation possibilities.


Corticosterone Reptile Mitochondrial efficiency Allostatic overload ROS emission and ATP production Oxygen consumption 



We are thankful to field assistants and technical staff at CEREEP-Ecotron IleDeFrance for their support, especially Hugo Mell. This study was funded by the Centre National de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (ANR-13-JSV7-0011-01 to S.M.) and the Région Île-de-France R2DS program (Grant 2013-08 to S.M., J.F.L.G. and R.J.). The authors declare no competing or financial interests.

Author contribution statement

YV, SM, and JFLG conceived, designed the study, and analyzed the data. RJ ensured animal husbandry, hormonal treatment and performed the statistical analyses. CH ensured plasma corticosterone measurements. DR and CR conceived and conducted the bioenergetics studies and performed the ROS production assessment. YV, SM, and JFLG wrote the manuscript; other authors provided editorial advice.

Supplementary material

442_2017_3933_MOESM1_ESM.pptx (258 kb)
Supplementary material 1 (PPTX 257 kb)


  1. Andres AM, Stotland A, Queliconi BB, Gottlieb RA (2015) A time to reap, a time to sow: mitophagy and biogenesis in cardiac pathophysiology. J Mol Cell Cardiol 78:62–72CrossRefPubMedGoogle Scholar
  2. Artacho P, Jouanneau I, Le Galliard JF (2013) Interindividual variation in thermal sensitivity of maximal sprint speed, thermal behavior, and resting metabolic rate in a lizard. Physiol Biochem Zool 86:458–469CrossRefPubMedGoogle Scholar
  3. Arvier M, Lagoutte L, Johnson G, Dumas JF, Sion B, Grizard G, Malthiery Y, Simard G, Ritz P (2007) Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment. Am J Physiol Endocrinol Metab 293:E1320–E1324CrossRefPubMedGoogle Scholar
  4. Beavis AD, Lehninger AL (1986) The upper and lower limits of the mechanistic stoichiometry of mitochondrial oxidative phosphorylation: stoichiometry of oxidative phosphorylation. Eur J Biochem 158:315–322CrossRefPubMedGoogle Scholar
  5. Brand MD (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35:811–820CrossRefPubMedGoogle Scholar
  6. Brand MD (2005) The efficiency and plasticity of mitochondrial energy transduction. Biochem Soc Trans 33:897–904CrossRefPubMedGoogle Scholar
  7. Brown JH, Gillooly JF, Allen AP, Savage VN, West GB (2004) Toward a metabolic theory of ecology. Ecology 85:1771–1789CrossRefGoogle Scholar
  8. Caro P, Gomez J, Sanz A, Portero-Otin M, Pamplona R, Barja G (2007) Effect of graded corticosterone treatment on aging-related markers of oxidative stress in rat liver mitochondria. Biogerontology 8:1–11CrossRefPubMedGoogle Scholar
  9. Chida Y, Sudo N, Kubo C (2006) Does stress exacerbate liver disease? J Gastroenter Hepatol 20:202–208CrossRefGoogle Scholar
  10. Cote J, Clobert J, Meylan S, Fitze PS (2006) Experimental enhancement of corticosterone levels positively affects subsequent male survival. Horm Behav 49:320–327CrossRefPubMedGoogle Scholar
  11. Cote J, Meylan S, Clobert J, Voituron Y (2010) Carotenoid-based coloration, oxidative stress and corticosterone in common lizards. J Exp Biol 213:2116–2124CrossRefPubMedGoogle Scholar
  12. Crossin GT, Love OP, Cooke SJ, Williams TD (2016) Glucocorticoid manipulations in free-living animals: considerations of dose delivery, life-history context and reproductive state. Funct Ecol 30:116–125CrossRefGoogle Scholar
  13. Dauphin-Villemant C, Xavier F (1987) Nychthemeral variations of plasma corticosteroids in captive female Lacerta vivipara Jacquin: influence of stress and reproductive state. Gen Comp Endocrinol 67:292–302CrossRefPubMedGoogle Scholar
  14. Desquiret V et al (2006) Dinitrophenol-induced mitochondrial uncoupling in vivo triggers respiratory adaptation in HepG2 cells. Biochem Biophys Acta 1757:21–30PubMedGoogle Scholar
  15. Dhabhar FS, McEwen BS, Spencer RL (1997) Adaptation to prolonged or repeated stress—comparison between rat strains showing intrinsic differences in reactivity to acute stress. Neuroendocrinology 65:360–368CrossRefPubMedGoogle Scholar
  16. Dowling DK, Simmons LW (2009) Reactive oxygen species as universal constraints in life-history evolution. Proc Biol Sci 276:1737–1745CrossRefPubMedCentralPubMedGoogle Scholar
  17. Du J et al (2009) Dynamic regulation of mitochondrial function by glucocorticoids. Proc Natl Acad Sci USA 106:3543–3548CrossRefPubMedCentralPubMedGoogle Scholar
  18. Duclos M, Gouarne C, Martin C, Rocher C, Mormede P, Letellier T (2004) Effects of corticosterone on muscle mitochondria identifying different sensitivity to glucocorticoids in Lewis and Fischer rats. Am J Physiol 286:E159–E167Google Scholar
  19. Dumas JF et al (2003) Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone. Br J Nutr 90:969–977CrossRefPubMedCentralPubMedGoogle Scholar
  20. Durant SE, Romero LM, Talent LG, Hopkins WA (2008) Effect of exogenous corticosterone on respiration in a reptile. Gen Comp Endocrinol 156:126–133CrossRefPubMedGoogle Scholar
  21. Glazier DS (2015) Is metabolic rate a universal ‘pacemaker’ for biological processes? Biol Rev 90:377–407CrossRefPubMedGoogle Scholar
  22. Isaksson C, Sheldon BC, Uller T (2011) The challenges of integrating oxidative stress into life-history biology. Bioscience 61:194–202CrossRefGoogle Scholar
  23. Jani MS, Telang SD, Katyare SS (1991) Effect of corticosterone treatment on energy metabolism in rat liver mitochondria. J Steroid Biochem Mol Biol 38:587–591CrossRefPubMedGoogle Scholar
  24. Kimberg DV, Loud AV, Wiener J (1968) Cortisone-induced alterations in mitochondrial function and structure. J Cell Biol 37:63–79CrossRefPubMedCentralPubMedGoogle Scholar
  25. Kooijman SALM (2010) Dynamic energy budget theory for metabolic organisation, 3rd edn. Cambridge University Press, CambridgeGoogle Scholar
  26. Liang SW et al (2017) Seasonal variation of metabolism in lizard Phrynocephalus vlangalii at high altitude. Comp Biochem Physiol A 203:341–347CrossRefGoogle Scholar
  27. Lighton JRB (2008) Measuring metabolic rates: a manual for scientists. Oxford University Press, OxfordCrossRefGoogle Scholar
  28. Mason RT (1992) Reptilian pheromones. In: Gans C, Crews D (eds) Biology of the Reptilia, vol 18. University of Chicago Press, Chicago, pp 114–228Google Scholar
  29. McEwen BS (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87:873–904CrossRefPubMedGoogle Scholar
  30. McEwen BS, Wingfield JC (2003) The concept of allostasis in biology and biomedicine. Horm Behav 43:2–15CrossRefPubMedGoogle Scholar
  31. Metcalfe NB, Alonso-Alvarez C (2010) Oxidative stress as a life-history constraint: the role of reactive oxygen species in shaping phenotypes from conception to death. Funct Ecol 24:984–996CrossRefGoogle Scholar
  32. Meylan S, Clobert J (2005) Is corticosterone-mediated phenotype development adaptive? Maternal corticosterone treatment enhances survival in male lizards. Horm Behav 48:44–52CrossRefPubMedGoogle Scholar
  33. Meylan S, Dufty AM, Clobert J (2003) The effect of transdermal corticosterone application on plasma corticosterone levels in pregnant Lacerta vivipara. Comp Biochem Physiol A Mol Integr Physiol 134:497–503CrossRefPubMedGoogle Scholar
  34. Meylan S, Haussy C, Voituron Y (2010) Physiological actions of corticosterone and its modulation by an immune challenge in reptiles. Gen Comp Endocrinol 169:158–166CrossRefPubMedGoogle Scholar
  35. Miles DB, Calsbeek R, Sinervo B (2007) Corticosterone, locomotor performance, and metabolism in side-blotched lizards (Uta stansburiana). Horm Behav 51:548–554CrossRefPubMedGoogle Scholar
  36. Monaghan P, Metcalfe NB, Torres R (2009) Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation. Ecol Lett 12:75–92CrossRefPubMedGoogle Scholar
  37. Monternier PA, Marmillot V, Rouanet JL, Roussel D (2014) Mitochondrial phenotypic flexibility enhances energy savings during winter fast in king penguin chicks. J Exp Biol 217:2691–2697CrossRefPubMedGoogle Scholar
  38. Morici LA, Elsey RM, Lance VA (1997) Effects of long-term corticosterone implants on growth and immune function in juvenile alligators, Alligator mississippiensis. J Exp Zool 279:156–162CrossRefPubMedGoogle Scholar
  39. Nisbet RM, Jusup M, Klanjscek T, Pecquerie L (2012) Integrating dynamic energy budget (DEB) theory with traditional bioenergetic models. J Exp Biol 215:892–902CrossRefPubMedGoogle Scholar
  40. Palacios MG, Sparkman AM, Bronikowski AM (2012) Corticosterone and pace of life in two life-history ecotypes of the garter snake Thamnophis elegans. Gen Comp Endocrinol 175:443–448CrossRefPubMedGoogle Scholar
  41. Pandya JD, Agarwal NA, Katyare SS (2004) Effect of dexamethasone treatment on oxidative energy metabolism in rat liver mitochondria during postnatal developmental periods. Drug Chem Toxicol 27:389–403CrossRefPubMedGoogle Scholar
  42. Picard M, Juster RP, McEwen BS (2014) Mitochondrial allostatic load puts the ‘gluc’ back in glucocorticoids. Nat Rev Endocrinol 10:303–310CrossRefPubMedGoogle Scholar
  43. Price CA et al (2012) Testing the metabolic theory of ecology. Ecol Lett 15:1465–1474CrossRefPubMedGoogle Scholar
  44. Psarra AM, Sekeris CE (2011) Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: role of the mitochondrial glucocorticoid receptor. Biochem Biophys Acta 1813:1814–1821CrossRefPubMedGoogle Scholar
  45. Ricklefs RE, Wikelski M (2002) The physiology-life history nexus. Trends Ecol Evol 17:462–468CrossRefGoogle Scholar
  46. Robert KA, Bronikowski AM (2010) Evolution of senescence in nature: physiological evolution in populations of garter snake with divergent life histories. Am Nat 175:E147–E159CrossRefGoogle Scholar
  47. Roma LP, Souza KL, Carneiro EM, Boschero AC, Bosqueiro JR (2012) Pancreatic islets from dexamethasone-treated rats show alterations in global gene expression and mitochondrial pathways. Gen Physiol Biophys 31:65–76CrossRefPubMedGoogle Scholar
  48. Romero LM, Dickens MJ, Cyr NE (2009) The reactive scope model—a new model integrating homeostasis, allostasis, and stress. Horm Behav 55:375–389CrossRefPubMedGoogle Scholar
  49. Roussel D, Dumas JF, Simard G, Malthiery Y, Ritz P (2004) Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment. Biochem J 382:491–499CrossRefPubMedCentralPubMedGoogle Scholar
  50. Salin K, Luquet E, Rey B, Roussel D, Voituron Y (2012a) Alteration of mitochondrial efficiency affects oxidative balance, development and growth in frog (Rana temporaria) tadpoles. J Exp Biol 215:863–869CrossRefPubMedGoogle Scholar
  51. Salin K, Roussel D, Rey B, Voituron Y (2012b) David and goliath: a mitochondrial coupling problem? J Exp Zool A 317:283–293CrossRefGoogle Scholar
  52. Salin K, Auer SK, Rey B, Selman C, Metcalfe NB (2015) Variation in the link between oxygen consumption and ATP production, and its relevance for animal performance. Proc Biol Sci 282:20151028CrossRefPubMedCentralPubMedGoogle Scholar
  53. Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89PubMedGoogle Scholar
  54. Sinervo B (1999) Mechanistic analysis of natural selection and a refinement of lack’s and William’s principles. Am Nat 154:S26–S42CrossRefGoogle Scholar
  55. Sinervo B, DeNardo DF (1996) Costs of reproduction in the wild: path analysis of natural selection and experimental tests of causation. Evolution 50:1299–1313CrossRefPubMedGoogle Scholar
  56. Sommer AM, Portner HO (2004) Mitochondrial function in seasonal acclimatization versus latitudinal adaptation to cold in the lugworm Arenicola marina (L.). Physiol Biochem Zool 77:174–186CrossRefPubMedGoogle Scholar
  57. Strack AM, Bradbury MJ, Dallman MF (1995) Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue. Am J Physiol 268:R183–R191PubMedGoogle Scholar
  58. Team RDC (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  59. Zera AJ, Potts J, Kobus K (1998) The physiology of life-history trade-offs: experimental analysis of a hormonally induced life-history trade-off in Gryllus assimilis. Am Nat 152:7–23CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Laboratoire d’Ecologie des Hydrosystèmes Naturels et Anthropisés (U.M.R. CNRS 5023)Université Claude Bernard Lyon1, Université de LyonVilleurbanne CedexFrance
  2. 2.Institut d’Ecologie et des Sciences, de l’Environnement de Paris (iEES Paris)-UPMC-CNRSParis Cedex 05France
  3. 3.Ecole Normale SupérieurePSL Research University, CNRS, Centre de recherche en écologie expérimentale et prédictive (CEREEP-Ecotron IleDeFrance), UMS 3194Saint-Pierre-Lès-NemoursFrance
  4. 4.ESPE de Paris, Université Sorbonne Paris IVParisFrance

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