A profile of carbohydrate metabolites in the fasting northern elephant seal Cory D. Champagne a, c, ⁎, Segal M. Boaz b , Melinda A. Fowler a , Dorian S. Houser c , Daniel P. Costa a , Daniel E. Crocker b a Dept. of Ecology and Evolutionary Biology, University of California, Santa Cruz, CA, USA b Dept. of Biology, Sonoma State University, Rohnert Park, CA, USA c National Marine Mammal Foundation, San Diego, CA, USA abstract article info Article history: Received 27 November 2012 Received in revised form 23 February 2013 Accepted 25 February 2013 Available online 14 March 2013 Keywords: Fasting Lactation Development Pinnipedia Metabolomics Glucoregulatory hormones Northern elephant seals endure prolonged periods of food deprivation at multiple life-history stages and simultaneous with energetically costly activities—including reproduction and development. Most mammals decrease their energy expenditure while fasting, with simultaneous reductions in gluconeogenesis and circu- lating glucose concentration. Paradoxically, elephant seals maintain high rates of both energy expenditure and gluconeogenesis, and high blood glucose concentrations throughout fasting. We therefore characterized the suite of changes that occur in carbohydrate metabolites during fasting in northern elephant seals. Using a broad-based metabolomics platform we investigated fasting during two states—lactation in adult females and the post-weaning developmental period in pups. A total of 227 metabolites were detected in seal plasma; 31 associated with carbohydrate metabolism were analyzed in the present study. Several compounds showed similar responses during lactation and the post-weaning fast (e.g. glycerol and mesaconate) whereas other compounds displayed quite different abundances between groups (e.g. citrate and pyruvate). This work found that, while the changes that occur with fasting were frequently similar in lactating females and developing pups, the relative abundance of compounds often varied markedly. These differences suggest that the metabolic strategies used to endure prolonged fasts are influenced by life-history or nutrient constraints. © 2013 Elsevier Inc. All rights reserved. 1. Introduction Nearly all vertebrates experience changes in food availability over time. Some animals have incorporated fasting as a regular component of their life-histories and several mammalian groups have coupled fasting with energetically intensive processes such as breeding, lacta- tion, and neonatal development (Castellini and Rea, 1992; Champagne et al., 2012a). These energetically intensive processes require significant drains on stored nutrient reserves acquired during previous foraging events. Fasting leads to physiological responses that protect body tissues from degradation until feeding is resumed. At the onset of fasting (stage I) metabolic rate declines and stored lipids are mobilized as the body shifts to a fat-based metabolism (Cahill, 1970). The progres- sion of fasting is characterized by the stabilization of the metabolic alterations that occur in stage I through depressed overall metabolic rate and continued reliance on lipid oxidation (stage II). These shifts in nutrient use associated with prolonged fasting deplete expendable fat reserves while minimizing protein loss (Goodman et al., 1980; Henry et al., 1988). Many tissues, however, including the central nervous system, erythrocytes, and the renal medulla, are glucose- dependent and cannot use lipid as an energy source. Some catabolism of lean tissue is therefore usually required to provide amino acid substrates for gluconeogenesis, replenishing the glucose oxidized by these glucose-dependent tissues. Terminal starvation (stage III) occurs once expendable nutrient reserves are depleted or the loss of protein to meet gluconegenic demand results in organ failure (Cahill, 1970). Thus, maintaining adequate circulating glucose con- centrations is an important challenge to fasting animals, potentially limiting their tolerance to prolonged fasting. Northern elephant seals (Mirounga angustirostris) endure prolonged fasts at multiple life stages. Between foraging trips to sea, elephant seals haul-out twice each year at rookeries in coastal and near-shore islands of western North America. Females haul-out each winter (Dec–Feb) and give birth to a single pup; the subsequent lactation period lasts approximately 26 days (McDonald and Crocker, 2006). During lacta- tion, females lose over a third of their initial body mass and up to 50% of their total body energy (Crocker et al., 2001). Pups may consume 4.5 kg milk per day (Ortiz et al., 1984) and triple in size from b 40 kg at birth to over 120 kg at weaning (Crocker et al., 2001). Lactation ends and pups are weaned abruptly when females return to sea. Pups then undergo a long post-weaning fast, often over two months, before they depart for their initial foraging trip to sea. Pups continue to develop after weaning; this development requires significant tissue Comparative Biochemistry and Physiology, Part D 8 (2013) 141–151 ⁎ Corresponding author at: National Marine Mammal Foundation, 2240 Shelter Island Dr, Bldg 200, San Diego, CA 92106, USA. Tel.: +1 707 321 6113. E-mail address: champagn@biology.ucsc.edu (C.D. Champagne). 1744-117X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cbd.2013.02.002 Contents lists available at SciVerse ScienceDirect Comparative Biochemistry and Physiology, Part D journal homepage: www.elsevier.com/locate/cbpd