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Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals (Mirounga angustirostris)

Abstract

Elephant seals maintain rates of endogenous glucose production (EGP) typical of post-absorptive mammals despite enduring prolonged periods of food deprivation concurrent with low rates of glucose oxidation. These high rates of EGP suggest extensive glucose recycling during fasting. We investigated lactate metabolism in fasting elephant seals to assess its role in glucose recycling. Whole-animal glucose and lactate fluxes were measured as the rates of appearance of glucose and lactate (Ra gluc and Ra lac, respectively) using a primed constant infusion of [U-14C] lactate and [6-3H] glucose, and we calculated the minimum contribution of lactate to gluconeogenesis (GNG lac). Ra lac was high compared to resting values in other species (3.21 ± 0.71 mmol min−1* kg−1), did not change between 14 ± 1 and 31 ± 8 days of fasting and varied directly with Ra glu. The minimum GNG lac was 44.6 ± 6.0 % of EGP, varied directly with plasma lactate levels, and did not change over the fast. Ra lac and Ra glu both varied directly with plasma insulin concentrations. These data suggest that lactate is the predominant gluconeogenic precursor in fasting elephant seals and that high rates of glucose recycling through Cori cycle activity contribute to the maintenance of EGP during fasting. High levels of Cori cycle activity and EGP may be important components of metabolic adaptations that maintain glucose production while avoiding ketosis during extended fasting or are related to sustained metabolic alterations associated with extended breath-holds in elephant seals.

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Abbreviations

EGP:

Enogenous glucose production

GNG:

Gluconeogenesis

Ra:

Rate of appearance

SA:

Specific activity

References

  1. Ahlquist DA, Nelson RA, Steiger DL, Jones JD, Ellefson RD (1984) Glycerol metabolism in the hibernating black bear. J Comp Physiol B 155:75–79

    Article  CAS  Google Scholar 

  2. Apple FS, McGue MK (1983) Serum enzyme changes during marathon training. Am J Clin Pathol 79:716–719

    PubMed  CAS  Google Scholar 

  3. Aragones J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170–180

    PubMed  Article  CAS  Google Scholar 

  4. Aragones J, Fraisl P, Baes M, Carmeliet P (2009) Oxygen sensors at the crossroads of metabolism. Cell Metab 9:13–22

    Article  Google Scholar 

  5. Baird GD, Van der Walt JG, Bergman EN (1983) Whole-body metabolism of glucose and lactate in productive sheep and cows. Br J Nutr 50:249–265

    Google Scholar 

  6. Bergman BC, Horning MA, Casazza GA, Wolfe EE, Butterfield GE, Brooks GA (2000) Endurance training increases gluconeogenesis during rest and exercise in men. Am J Physiol 278:E244–E251

    CAS  Google Scholar 

  7. Blackwell SB, Le Boeuf BJ (1993) Developmental aspects of sleep apnoea in northern elephant seals, Mirounga angustirostris. J Zool Lond 231:437–447

    Google Scholar 

  8. Castellini MA, Rea LD (1992) The biochemistry of natural fasting at its limits. Experientia 48:575–582

    PubMed  Article  CAS  Google Scholar 

  9. Castellini MA, Castellini M, Kirby VL (1992) Effects of standard anticoagulants and storage procedures on plasma glucose values in seals. J Am Vet Med Assn 201:145–148

    CAS  Google Scholar 

  10. Champagne CD, Houser DS, Crocker DE (2005) Glucose production and substrate cycle activity in a fasting adapted animal, the northern elephant seal. J Exp Biol 208:859–868

    PubMed  Article  CAS  Google Scholar 

  11. Champagne CD, Houser DS, Crocker DE (2006) Glucose metabolism during lactation in a fasting animal, the northern elephant seal. Am J Physiol Reg I 291:1129–1137

    Article  Google Scholar 

  12. Champagne CD, Houser DS, Costa DP, Crocker DE (2012a) The effects of handling and anesthetic agents on the stress response and carbohydrate metabolism in northern elephant seals. PLoS One 7(5):e36728

    PubMed  Article  Google Scholar 

  13. Champagne CD, Crocker DE, Fowler MA and Houser DS (2012b) Fasting physiology of the pinnipeds: the challenges of fasting while maintaining high energy expenditure and nutrient delivery for lactation. In: The comparative physiology of starvation, fasting and food limitation. (ed. M.D. McCue). Springer, Berlin, pp. 309–336

  14. Champagne CD, Houser DS, Fowler MA, Costa DP, Crocker DE (2012c) Gluconeogenesis is associated with high rates of tricarboxylic acid and pyruvate cycling in fasting northern elephant seals. Am J Physiol 303:340–352

    Google Scholar 

  15. Cherel Y, Stahl JC, Le Maho Y (1987) Ecology and physiology of fasting in king penguin chicks. Auk 104:254–262

    Google Scholar 

  16. Cherel Y, Robin JP, Walch O, Karmann H, Netchitailo P, Le Maho Y (1988) Fasting in king penguin: hormonal and metabolic changes during breeding. Am J Physiol 254:R170–177

    PubMed  CAS  Google Scholar 

  17. Cook DR (1977) Detection of influential observation in linear regression. Technometrics 19:15–18

    Article  Google Scholar 

  18. Consoli A, Kennedy F, Miles J, Gerich J (1987) Determination of Kreb’s Cycle metabolic carbon exchange In Vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man. J Clin Invest 80:1303–1310

    PubMed  Article  CAS  Google Scholar 

  19. Crocker DE, Williams JD, Costa DP, Le Boeuf BJ (2001) Maternal traits and reproductive effort in northern elephant seals. Ecology 82:3541–3555

    Article  Google Scholar 

  20. Davis RW (1983) Lactate and glucose metabolism in the resting and diving harbor seal (Phoca vitulina). J Comp Physiol B 153:275–288

    Article  CAS  Google Scholar 

  21. Davis RW, Castellini MA, Williams TM, Kooyman GL (1991) Fuel homeostasis in the harbor seal during submerged swimming. J Comp Physiol B 160:627–635

    PubMed  Article  CAS  Google Scholar 

  22. DiGirolamo M, Fried SK (1987) In vitro metabolism of adipocytes. In: Hausman GJ, Martin R (eds) Biology of the adipocyte research approaches. Van Nostrand Reinhold Co., NY, pp 120–147

    Google Scholar 

  23. DiGirolamo M, Newby FD, Lovejoy J (1992) Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB J 6:2405–2412

    PubMed  CAS  Google Scholar 

  24. Edwards LJ, Muller KE, Wolfinger RD, Qaqish BF, Schabenberger O (2008) An R 2 statistic for fixed effects in the linear mixed model. Stat Med 27:6137–6157

    PubMed  Article  Google Scholar 

  25. Feneberg R, Sparber M, Veldhuis JD, Mehls O, Ritz E, Schaefer F (1999) Synchronous fluctuations of blood insulin and lactate concentrations in humans. J Clin Endoc Met 84:220–227

    Article  CAS  Google Scholar 

  26. Fowler MA, Champagne CD, Houser DS, Crocker DE (2008) Hormonal regulation of glucose clearance in lactating northern elephant seals (Mirounga angustirostris). J Exp Biol 211:2943–2949

    PubMed  Article  Google Scholar 

  27. Geiser F (1998) Evolution of daily torpor and hibernation in birds and mammals: Importance of body size. Clin Exp Pharmacol 25:736–740

    Article  CAS  Google Scholar 

  28. Geiser F (2004) Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66:239–274

    PubMed  Article  CAS  Google Scholar 

  29. Gladden LB (2008) A ‘‘lactatic’’ perspective on metabolism. Med Sci Sports Exerc 40:477–485

    PubMed  Article  CAS  Google Scholar 

  30. Groscolas R, Rodriguez A (1982) Glucose and lactate kinetics and interrelations in an Antarctic bird (emperor penguin). Am J Physiol Reg I 242:458–464

    Google Scholar 

  31. Groscolas R (1986) Changes in body mass, body temperature and plasma fuel level during the natural breeding fast in male and female emperor penguins (Aptendytes forsteri). J Comp Physiol B 156:521–527

    Article  Google Scholar 

  32. Guppy M, Withers P (1999) Metabolic depression in animals: physiological perspectives and biochemical generalizations. Biol Rev Camb Philos 74:1–40

    Article  CAS  Google Scholar 

  33. Holloszy JO, Coyle EF (1984) Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56:831–838

    PubMed  CAS  Google Scholar 

  34. Houser DS, Costa DP (2001) Protein catabolism in suckling and fasting northern elephant seal pups (Mirounga angustirostris). J Comp Physiol B 171:635–642

    PubMed  Article  CAS  Google Scholar 

  35. Houser DS, Champagne CD, Crocker DE (2007) Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals. Am J Physiol 293:R2376–R2381

    Google Scholar 

  36. Houser DS, Tift MS, Cory Champagne CD, Crocker DE (2012) Glucose oxidation and non-oxidative glucose disposal during prolonged fasts of the northern elephant seal pup (Mirounga angustirostris). Am J Physiol 303:562–570

    Google Scholar 

  37. Huie MJ, Casazza GA, Horning MA, Brooks GA (1996) Smoking increases conversion of lactate to glucose during submaximal exercise. J Appl Physiol 80:1554–1559

    PubMed  CAS  Google Scholar 

  38. Issekutz B, Shaw WAS, Issekutz AC (1976) Lactate metabolism in resting and exercising dogs. J Appl Physiol 40:312–319

    PubMed  CAS  Google Scholar 

  39. Iyer NV, Kotch LE, Agani F (1998) Cellular and developmental control of O2 homeostasis by hypoxia inducible factor 1. Genes Dev 12:149–162

    PubMed  Article  CAS  Google Scholar 

  40. Jansson P, Larsson A, Smith U, Lonnroth P (1994) Lactate release from the subcutaneous tissue in lean and obese men. J Clin Invest 93:240–246

    PubMed  Article  CAS  Google Scholar 

  41. Jenssen T, Nurjhan N, Consoli A, Gerich JE (1993) Dose-response effects of lactate infusions on gluconeogenesis from lactate in normal man. Eur J Clin Invest 23:448–454

    PubMed  Article  CAS  Google Scholar 

  42. Katz J, Tayek JA (1998) Gluconeogenesis and the Cori cycle in 12-, 20, and 40 h-fasted humans. Am J Physiol Endoc M 275:E537–E542

    CAS  Google Scholar 

  43. Katz J, Wals P, Paul Lee WN (1993a) Isotopomer studies of gluconeogenesis and the Krebs cycle with 13C-labeled lactate. J Biol Chem 268:25509–25521

    PubMed  CAS  Google Scholar 

  44. Katz SD, Bleiberg B, Wexler J, Steinberg JJ, Lejemtel TH (1993b) Lactate turnover at rest and during submaximal exercise in patients with heart failure. J Appl Physiol 75:1974–1979

    PubMed  CAS  Google Scholar 

  45. Kirby VL, Ortiz CL (1994) Hormones and fuel regulation in fasting elephant seals. In: Le Boeuf BJ, Laws RM (eds) Elephant seals: population ecology, behavior, and physiology. University of California Press, Berkeley, pp 374–386

    Google Scholar 

  46. Landau BR, Wahren J, Ekberg K, Previs SF, Yang D, Brunengraber H (1998) Limitations in estimating gluconeogenesis and Cori cycling from mass isotopomer distributions using [U-13C6] glucose. Am J Physiol-Endoc M 274:954–961

    Google Scholar 

  47. Lovejoy J, Mellen B, DiGirolamo M (1990) Lactate generation following glucose ingestion. Relation to obesity, carbohydrate tolerance and insulin sensitivity. Int J Obes 14:843–855

    PubMed  CAS  Google Scholar 

  48. McCue MD (2010) Starvation physiology: reviewing the different strategies animals use to survive a common challenge. Comp Biochem Physiol A 156:1–18

    Google Scholar 

  49. Meir JU, Champagne CD, Costa DP, Williams CL, Ponganis PJ (2009) Extreme hypoxemic tolerance and blood oxygen depletion in diving elephant seals. Am J Physiol 297:R927–R939

    CAS  Google Scholar 

  50. Miller BF, Fattor JA, Jacobs KA, Horning MA, Navazio F, Lindinger MI, Brooks GA (2002) Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion. J Physiol 544:963–975

    PubMed  Article  CAS  Google Scholar 

  51. Nelson RA, Folk GE, Pfeiffer EW, Craighead JJ, Jonkel CJ (1980) Behavior, biochemistry, and hibernation in black, grizzly, and polar bears. In Conf Bear Res Manage 5:284–290

    Google Scholar 

  52. Noren DP, Crocker DE, Williams TM, Costa DP (2003) Energy reserve utilization in northern elephant seal (Mirounga angustirostris) pups during the postweaning fast: size does matter. J Comp Physiol B 173:443–454

    Google Scholar 

  53. Ortiz RM, Houser DS, Wade CE, Ortiz CL (2003) Hormonal changes associated with the transition between nursing and natural fasting in northern elephant seals (Mirounga angustirostris). Gen Comp Endocr 130:78–83

    PubMed  Article  CAS  Google Scholar 

  54. Qvisth V, Hagstrom-Toft E, Moberg E, Sjoberg S, Bolinder J (2006) Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women. Am J Physiol 292:E709–E714

    Google Scholar 

  55. Packard GC, Boardman TJ (1999) The use of percentages and size-specific indices to normalize physiological data for variation in body size: wasted time, wasted effort? Comp Biochem Physiol A 122(1):37–44

    Article  Google Scholar 

  56. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC (2006) HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3:187–197

    PubMed  Article  CAS  Google Scholar 

  57. Ponganis PJ, Kreutzer U, Stockard TK, Lin PC, Sailasuta N, Tran TK, Hurd R, Jue T (2008) Blood flow and metabolic regulation in seal muscle during apnea. J Exp Biol 211:3323–3332

    PubMed  Article  CAS  Google Scholar 

  58. Thorson PH, Le Boeuf BJ (1994) Developmental aspects of diving in northern elephant seal pups. In: Le Boeuf BJ, Laws RM (eds) Elephant seals: population ecology, behavior, and physiology. University of California Press, Berkeley, pp 271–289

    Google Scholar 

  59. Tøien Ø, Blake J, Edgar DM, Grahn DA, Heller HC, Barnes BM (2011) Hibernation in black bears: independence of metabolic suppression from body temperature. Science 331:906–909

    PubMed  Article  Google Scholar 

  60. Vázquez-Medina JP, Crocker DE, Forman HJ, Ortiz RM (2010) Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups. J Exp Biol 213:2524–2530

    Google Scholar 

  61. Vázquez-Medina JP, Zenteno-Savín T, Tift MS, Forman HJ, Crocker DE, Ortiz RM (2011) Apnea stimulates the adaptive response to oxidative stress in elephant seal pups. J Exp Biol 214:4193–4200

    PubMed  Article  Google Scholar 

  62. Viscarra JA, Vázquez-Medina JP, Crocker DE, Ortiz RM (2011) Glut4 is upregulated despite decreased insulin signaling during prolonged fasting in northern elephant seal pups. Am J Physiol-Reg I 300:R150–R154

    CAS  Google Scholar 

  63. Weinman E, Strisower E, Chaikoff I (1952) Conversion of fatty acids to carbohydrate: application of isotope to this problem and role of Krebs cycle as a synthesis pathway. Physiol Rev 37:252–272

    Google Scholar 

  64. Wolfe RR, Chinkes DL (2005) Isotope tracers in metabolic research: Principle and practice of kinetic analysis. Hoboken, NJ

    Google Scholar 

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Acknowledgments

The authors would like to thank Mike Tift for assistance in the field. The authors would also like to thank the staff and rangers of Año Nuevo State Park for logistical support. This work was performed under National Marine Fisheries Service permit 87-1743. The research was supported by NSF Grant #0818018. Any opinions and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

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Correspondence to Daniel E. Crocker.

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Communicated by H.V. Carey.

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Tavoni, S.K., Champagne, C.D., Houser, D.S. et al. Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals (Mirounga angustirostris). J Comp Physiol B 183, 537–546 (2013). https://doi.org/10.1007/s00360-012-0720-5

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Keywords

  • Fasting
  • Pinniped
  • Lactate
  • Endogenous glucose production
  • Cori cycle