Abstract
Mammals with increased requirements for adipose tissue stores, such as marine mammals, have altered nutrient allocation priorities compared to many terrestrial mammals and thus the physiological response to undernutrition (low nutritional status) and realimentation (refeeding) may differ. Key regulators of nutrient allocation and tissue specific growth include metabolic hormones of the somatotropic axis, growth hormone (GH) and insulin-like growth factor (IGF)-I, as well as satiety and adipose promoting ghrelin and the stress hormone cortisol. Longitudinal measurements of metabolic hormones, blood metabolites, and morphometrics were collected over a 10-week period in twelve (male n = 3, female n = 9) harbor seal pups (< 6 weeks of age). Blood metabolites were used to indicate metabolic response during realimentation while morphometrics estimated tissue specific growth priorities. Harbor seal pups undergoing refeeding after nutritional deprivation show a preference for protein sparing despite severe malnutrition. Both BUN and total protein were negatively associated with GH and positively associated with IGF-I and ghrelin highlighting the importance of these metabolic hormones in the regulation of protein metabolism. While the response of the somatotropic axis to realimentation was typical of the mammalian pattern, the surprising increase of ghrelin across the study period suggests the priority of adipose accretion in addition to a possible mechanism regulating compensatory growth of vital adipose stores in a species, which prioritizes adipose accretion for survival.
Similar content being viewed by others
References
Bergendahl M, Vance ML, Iranmanesh A, Thorner MO, Veldhuis JD (1996) Fasting as a metabolic stress paradigm selectively amplifies cortisol secretory burst mass and delays the time of maximal nyctohemeral cortisol concentrations in healthy men. J Clin Endocrinol Metab 81(2):692–699
Bohn MK, Higgins V, Adeli K (2019) CALIPER paediatric reference intervals for the urea creatinine ratio in healthy children & adolescents. Clin Biochem 76:31–34. https://doi.org/10.1016/j.clinbiochem.2019.12.001
Bossart GD, Reidarson TH, Dierauf LA, Duffield DA (2001) Clinical pathology: blood collection. In: Dierauf LA, Gulland FM (eds) CRC handbook of marine mammal medicine, 2nd edn. CRC Press, Boca Raton, pp 384–390
Bowen WD (1991) Behavioural ecology of pinniped neonates. In: Renouf D (ed) The behaviour of pinnipeds. Chapman and Hall, London, pp 66–127
Breier BH (1999) Regulation of protein and energy metabolism by the somatotropic axis. Domest Anim Endocrinol 17:209–218
Breier BH, Bass JJ, Butler JH, Gluckman PD (1986) The somatotropic axis in young steers: influence of nutritional status on pulsatile release of growth hormone and circulating concentrations on insulin-like growth factor-I. J Endocrinol 111:209–215
Buonomo FC, Baile CA (1991) Influence of nutritional deprivation on insulin-like growth factor I, somatotropin, and metabolic hormones in swine. J Anim Sci 69:755–760
Castellini MA, Rea LD (1992) The biochemistry of natural fasting at its limits. Experientia 48(6):575–582
Champagne CD, Crocker DE, Fowler MA, Houser DS (2012) Fasting physiology of the pinnipeds: the challenges of fasting while maintaining high energy expenditure and nutrient delivery for lactation. In: McCue MD (ed) Comparative physiology of fasting, starvation, and food limitation. Springer, Berlin, pp 309–336
Costa DP, Ortiz CL (1982) Blood chemistry homeostasis during prolonged fasting in the northern elephant seal. Am J Physiol 242:R591–R595
Cottrell P, Jeffries S, Beck B, Ross P (2002) Growth and development in free-ranging harbor seal (Phoca vitulina) pups from southern British Columbia, Canada. Mar Mammal Sci 18(3):721–733
Counts D, Gwirtsman H, Carlsson L, Lesem M, Cutler G (1992) The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the insulin-like growth factors (IGFs), and the IGF-binding proteins. J Clin Endocrinol Metab 75(3):762–767
Crocker DE, Ortiz RM, Houser DS, Webb PM, Costa DP (2012) Hormone and metabolite changes associated with extended breeding fasts in male northern elephant seals (Mirounga angustirostris). Comp Biochem Physiol A 161:388–394. https://doi.org/10.1016/j.cbpa.2011.12.013
Crocker D, Wenzel B, Champagne C, Houser D (2017) Adult male northern elephant seals maintain high rates of glucose production during extended breeding fasts. J Comp Physiol B 187(8):1183–1192
Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346(21):1623–1630
Dailey RE, Fontaine CM, Avery JP (2016) Endocrine response to realimentation in young northern elephant seals (Mirounga angustirostris): indications for development of fasting adaptation. Gen Comp Endocrinol 235:130–135. https://doi.org/10.1016/j.ygcen.2016.06.009
Dantzer B, Swanson E (2012) Mediation of vertebrate life histories via insulin-like growth factor-1. Biol Rev 87(2):414–429
Djurhuus C, Gravholt C, Nielsen S, Pedersen S, Moller N, Schmitz O (2004) Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans. Am J Physiol Endocrinol Metab 286(3):E488–E494
Etherton TD (2004) Somatotropic function: the somatomedin hypothesis revisited. J Anim Sci 82(13):E239–E244
Fadely BS (1997) Investigations of harbor seal (Phoca vitulina) health status and body condition in the Gulf of Alaska. Doctoral dissertation. University of Alaska Fairbanks, AK
Frouin H, Haulena M, Akhurst LMF, Raverty SA, Ross PS (2013) Immune status and function in harbor seal pups during the course of rehabilitation. Vet Immunol Immunopathol 155:98–109. https://doi.org/10.1016/j.vetimm.2013.06.011
Fuglei E, Mustonen AM, Nieminen P (2004) Effects of season, food deprivation and re-feeding on leptin, ghrelin and growth hormone in arctic foxes (Alopex lagopus) on Svalbard, Norway. J Comp Physiol B 174:157–162
Greig DJ, Gulland FM, Harvey JT, Lonergan M, Hall AJ (2019) Harbor seal pup dispersal and individual morphology, hematology, and contaminant factors affecting survival. Mar Mammal Sci 35(1):187–209. https://doi.org/10.1111/mms.12541
Gulland FM, Dierauf DL, Rowles TK (2001) Marine mammal stranding networks. In: Dierauf LA, Gulland FM (eds) CRC handbook of marine mammal medicine, 2nd edn. CRC Press, Boca Raton, pp 45–67
Hall AJ (1998) Blood chemistry and hematology of gray seal (Halichoerus grypus) pups from birth to postweaning. J Zoo Wildl Med 29(4):401–407
Harding KC, Fujiwara M, Axberg Y, Harkonen T (2005) Mass-dependent energetics and survival in Harbour Seal pups. Funct Ecol 19:129–135
Higginson A, McNamara J, Houston A (2014) The starvation–predation trade-off shapes the strategic use of protein for energy during fasting. J Theor Biol 359:208–219
Hornick JL, Van Eenaeme C, Gérard O, Dufrasne I, Istasse L (2000) Mechanisms of reduced and compensatory growth. Domest Anim Endocrinol 19(2):121–132. https://doi.org/10.1016/S0739-7240(00)00072-2
Jennings JS, Wertz-Lutz AE, Pritchard RH, Weaver AD, Keisler DH, Bruns K (2011) Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain. J Anim Sci 89:3954–3972. https://doi.org/10.2527/jas.2010-3597
Kaiya H, Kangawa K, Miyazato M (2013) Update on ghrelin biology in birds. Gen Comp Endocrinol 190(1):170–175. https://doi.org/10.1016/j.ygcen.2013.04.014
Kaplan SA, Cohen P (2007) Review: the somatomedin hypothesis 2007: 50 years later. J Clin Endocrinol Metab 92(12):4529–4535
Kelso EJ, Champagne CD, Tift MS, Houser DS, Crocker DE (2012) Sex differences in fuel use and metabolism during development in fasting juvenile northern elephant seals. J Exp Biol 215(15):2637–2645
Keogh K, Waters SM, Kelly AK, Kenny DA (2015a) Feed restriction and compensatory growth in Holstein Friesian bulls: I. Effect on animal performance, muscle, fat and linear body measurements and slaughter characteristics. J Anim Sci. https://doi.org/10.2527/jas2014-8470
Keogh K, Waters S, Kelly A, Wylie A, Sauerwein H, Sweeney T, Kenny D (2015b) Feed restriction and realimentation in Holstein-Friesian bulls: II. Effect on blood pressure and systemic concentrations of metabolites and metabolic hormones. J Anim Sci 93(7):3590–3601. https://doi.org/10.2527/jas2014-8471
Keogh K, Waters S, Kelly A, Wylie A, Kenny D (2015c) Effect of feed restriction and subsequent re-alimentation on hormones and genes of the somatotropic axis in cattle. Physiol Genom 47(7):264–273. https://doi.org/10.1152/physiolgenomics.00134.2014
Kershaw JL, Hall AJ (2016) Seasonal variation in harbour seal (Phoca vitulina) blubber cortisol - A novel indicator of physiological state? Sci Rep. https://doi.org/10.1038/srep21889
Khani S, Tayek JA (2001) Cortisol increases gluconeogenesis in humans: its role in the metabolic syndrome. Clin Sci 101(6):739–747
Lander ME, Harvey JT, Gulland FM (2003) Hematology and serum chemistry comparisons between free-ranging and rehabilitated harbor seal (Phoca vitulina richardsi) pups. J Wildl Dis 39(3):600–609
Lavigne DM, Innes S, Worthy GAJ, Kovacs KM, Schmitz OJ, Hickie JP (1986) Metabolic rates of seals and whales. Can J Zool 64(2):279–284
Livingstone C (2013) Insulin-like growth factor-I (IGF-I) and clinical nutrition. Clin Sci 125(6):265–280
Markussen N, Ryg M, Øritsland N (1990) Energy requirements for maintenance and growth of captive harbour seals, Phoca vitulina. Can J Zool 68:423–426
Maxwell A, Butterwick R, Batt R, Camacho-Hübner C (1999) Serum insulin-like growth factor (IGF)-I concentrations are reduced by short-term dietary restriction and restored by refeeding in domestic cats (Felis catus). J Nutr 129(10):1879–1884
McCue MD (2010) Starvation physiology: reviewing the different strategies animals use to survive a common challenge. Comp Biochem Physiol A Mol Integr Physiol 156(1):1–18
Mellish JE, Iverson SJ (2001) Blood metabolites as indicators of nutrient utilization in fasting, lactating phocid seals: does depletion of nutrient reserves terminate lactation? Can J Zool 79(2):303–311
Muelbert MMC, Bowen WD, Iverson SJ (2003) Weaning mass affects changes in body composition and food intake in harbour seal pups during the first month of independence. Physiol Biochem Zool 76(3):418–427
Müller MJ, Enderle J, Pourhassan M, Braun W, Eggeling B, Lagerpusch M, Glüer C, Kehayias JJ, Kiosz D, Bosy-Westphal A (2015a) Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited. Am J Clin Nutr 102(4):807–819. https://doi.org/10.3945/ajcn.115.109173
Müller T, Nogueiras R, Andermann M, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH (2015b) Ghrelin. molecular. Metabolism 4(6):437–460. https://doi.org/10.1016/j.molmet.2015.03.005
Nakazato M, Mauakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S (2001) A role for ghrelin in the central regulation of feeding. Nature 409:194–198
Oki C, Atkinson S (2004) Diurnal patterns of cortisol and thyroid hormones in the Harbor seal (Phoca vitulina) during summer and winter seasons. Gen Comp Endocrinol 136(2):289–297
Ortiz RM, Wade CE, Ortiz CL, Talamantes F (2003a) Acutely elevated vasopressin increases circulating concentrations of cortisol and aldosterone in fasting northern elephant seal (Mirounga angustirostris) pups. J Exp Biol 206(16):2795–2802
Ortiz RM, Noren DP, Ortiz CL, Talamantes F (2003b) GH and ghrelin increase with fasting in a naturally adapted species, the northern elephant seal (Mirounga angustirostris). J Endocrinol 178:533–539
Ottosson M, Lonnroth P, Bjorntorp P, Eden S (2000) Effects of cortisol and growth hormone on lipolysis in human adipose tissue. J Clin Endocrinol Metab 85(2):799–803
Perez-Tilve D, Heppner K, Kirchner H, Lockie S, Woods S, Smiley D, Tschop M, Pfluger P (2011) Ghrelin-induced adiposity is independent of orexigenic effects. FASEB J 25(8):2814–2822
Perrone RD, Madias NE, Levey AS (1992) Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 38(10):1933–1953
Phomvisith O, Takahashi H, Mai H, Shiotsuka Y, Matsubara A, Sugino T, Mcmahon C, Etoh T, Fujino R, Furuse M, Gotoh T (2017) Effects of nutritional status on hormone concentrations of the somatotropin axis and metabolites in plasma and colostrum of Japanese Black cows. J Anim Sci 88(4):643–652
Purnell JQ, Weigle DS, Breen P, Cummings DE (2003) Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 88(12):5747–5752
Rea LD (1995) Prolonged fasting in pinnipeds. Doctoral dissertation, University of Alaska Fairbanks, AK
Renaville R, Hammadi M, Portetelle D (2002) Role of the somatotropic axis in the mammalian metabolism. Domest Anim Endocrinol 23:351–360
Richmond JP, Zinn SA (2009) Validation of heterologous radioimmunoassay (RIA) for growth hormone (GH) and insulin-like growth factor (IGF)-I in phocid, otariid, and cetacean species. Aquat Mammals 35(1):19–31
Richmond JP, Skinner J, Gilbert J, Mazzaro LM, Zinn SA (2008) Comparison of the somatotropic axis in free-ranging and rehabilitated harbor seal pups(Phoca vitulina). J Zoo Wildl Med 39(3):342–348
Richmond JP, Norris T, Zinn SA (2010) Re-alimentation in harbor seal pups: Effects on the somatotropic axis and growth rate. Gen Comp Endocrinol 165:286–292
Roletto J (1993) Hematology and serum chemistry values for clinically healthy and sick pinnipeds. J Zoo Wildl Med 24(2):145–157
Rollo C, Kajiura L, Wylie B, D'Souza S (1999) The growth hormone axis, feeding, and central allocative regulation: lessons from giant transgenic growth hormone mice. Can J Zool 77(12):1861–1873
Sangiao-Alvarellos S, Helmling S, Vázquez MJ, Klussmann S, Cordido F (2011) Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism. Mol Cell Endocrinol 335(2):177–188
Savino F, Lupica MM, Liguori SA, Fissore MF, Silvestro L (2012) Ghrelin and feeding behaviour in preterm infants. Early Human Dev 88:S51–S55
Scacchi M, Pincelli A, Cavagnini F (2003) Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa. Front Neuroendocrinol 24(3):200–224
Schulz TM, Bowen WD (2004) Pinniped lactation strategies: evaluation of data on maternal and offspring life history traits. Mar Mammal Sci 20(1):86–114
Schulz TM, Bowen WD (2005) The evolution of lactation strategies in pinnipeds: a phylogenetic analysis. Ecol Monogr 75(2):159–177
Song X, Jiao H, Zhao J, Wang X, Lin H (2019) Ghrelin serves as a signal of energy utilization and is involved in maintaining energy homeostasis in broilers. Gen Comp Endo 272:76–82. https://doi.org/10.1016/j.ygcen.2018.11.017
Strandberg U, Käkelä A, Lydersen C, Kovacs KM, Grahl-Nielsen O, Hyvärinen H, Käkelä R (2008) Stratification, composition, and function of marine mammal blubber: the ecology of fatty acids in marine mammals. Physiol Biochem Zool 81(4):473–485
Straus D, Takemoto C (1990) Effect of fasting on insulin-like growth factor-I (IGF-I) and growth hormone receptor mRNA levels and IGF-I gene transcription in rat liver. Mol Endocrinol 4(1):91–100
Tanaka M, Naruo T, Muranaga T et al (2002) Increased fasting plasma ghrelin levels in patients with bulimia nervosa. Eur J Endocrinol 146(6):R1–R3
Tanaka M, Nakahara T, Kojima S, Nakano T, Muranaga T, Nagai N, Ueno H, Nakazato M, Nozoe S, Naruo T (2004) Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa. Regul Pept 122:163–168
Thissen J, Underwood LE, Ketelslegers J (1999) Regulation of insulin-like growth factor-I in starvation and injury. Nutr Rev 57(6):167–176
Townsend FI, Gage LJ (2001) Hand-rearing and artificial milk formulas. In: Dierauf LA, Gulland FM (eds) CRC handbook of marine mammal medicine, 2nd edn. CRC Press, Boca Raton, pp 829–849
Trumble SJ, Castellini MA, Mau TL, Castellini JM (2006) Dietary and seasonal influences on blood chemistry and hematology in captive harbor seals. Mar Mammal Sci 22(1):104–123
Trumble SJ, O'Neil D, Cornick LA, Gulland F, Castellini MA, Atkinson S (2013) Endocrine changes in harbor seal (Phoca vitulina) pups undergoing rehabilitation. Zoo Biol 32(2):134–141
Tschop M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407(6806):908–913
Viscarra JA, Champagne CD, Crocker DE, Ortiz RM (2011) 5′AMP-activated protein kinase activity is increased in adipose tissue of northern elephant seal pups during prolonged fasting-induced insulin resistance. J Endocrinol 209:317–325. https://doi.org/10.1530/joe-11-0017
Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA (2004) Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol 180(2):247–255
Witte K, Driver J, Rosenberger T, Adler S, Siebert U (2014) Analysis of blood gases, serum fat and serum protein: a new approach to estimate survival chances of stranded Harbor seal (Phoca vitulina) pups from the German North Sea. Acta Vet Scand 56(1):10
Yakar S, Werner H, Rosen C (2018) 40 YEARS OF IGF1: Insulin-like growth factors: actions on the skeleton. J Mol Endocrinol 61(1):T115–T137
Acknowledgements
The authors would like to thank The Marine Mammal Center for their collaboration, providing serum samples, morphometric and diet data. The authors thank Cory D Champagne and two anonymous reviewers for comprehensive, through and constructive edits that vastly improved the quality and clarity of this manuscript. Animal protocols were reviewed and approved by the University of North Florida Institutional Animal Care and Use Committee (IACUC # 12-006W). The Marine Mammal Center is authorized by NOAA NMFS permit for Marine Mammal Health and Stranding Response Permit #18786. Funding for this project was provided by UNF Coastal Biology Program and laboratory start-up funds issued to J. Avery.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by H.V. Carey.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Dailey, R.E., Smith, K., Fontaine, C. et al. Response of metabolic hormones and blood metabolites to realimentation in rehabilitated harbor seal (Phoca vitulina) pups. J Comp Physiol B 190, 629–640 (2020). https://doi.org/10.1007/s00360-020-01290-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00360-020-01290-5