Abstract
Branched-chain amino acids, particularly leucine, are thought to activate nutrient sensing pathways in the hypothalamus that regulate food intake and energy homeostasis. In the light of recent controversial findings of leucine’s effect on energy homeostasis further clarification of the metabolic impact of dietary leucine supplementation is required. We examined the pharmacological and dietary effects of leucine on energy metabolism in the Djungarian hamster (Phodopus sungorus), a well-established model for studies of alterations in leptin sensitivity and energy metabolism. We acutely administered leucine into the lateral ventricle (1.1 μg) of hamsters to characterize whether leucine exhibits anorexigenic properties in this species as has been described in other rodents. Next the catabolic effect of dietary administered leucine via supplemented rodent diet (15 % leucine), drinking water (17 g/L leucine) and oral gavages (10 mg/day); as well as the effect of subcutaneously (0.1 and 3 mg/day) and intraperitoneally (0.1, 3 and 6 mg/day) injected leucine which avoids the gastrointestinal-track was analyzed. Centrally administered leucine reduced 24 h food intake (by 32 %) and body weight. Both parameters were also reduced in hamsters with leucine supplemented diet, but this catabolic response was based on a pronounced taste aversion to the leucine-diet. In all other experiments, dietary leucine and peripheral injections of leucine had no effect on food intake, body weight and basal blood glucose levels. Our data suggest that in the Djungarian hamster dietary leucine fails to exhibit catabolic effects that would override the evolutionary conserved adaptations of the species which is critical for its survival.
This is a preview of subscription content, access via your institution.
References
Blouet C, Jo YH, Li X, Schwartz GJ (2009) Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci 29(26):8302–8311
Buse MG, Reid SS (1975) Leucine. A possible regulator of protein turnover in muscle. J Clin Invest 56(5):1250–1261
Cangiano C, Laviano A, Meguid MM, Mulieri M, Conversano L, Preziosa I et al (1996) Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. J Natl Cancer Inst 88(8):550–552
Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC et al (2006) Hypothalamic mTOR signaling regulates food intake. Science 312(5775):927–930
Cota D, Matter EK, Woods SC, Seeley RJ (2008) The role of hypothalamic mammalian target of rapamycin complex 1 signaling in diet-induced obesity. J Neurosci 28(28):7202–7208
Fajans SS, Knopf RF, Floyd JC, Power L, Conn JW (1963) The experimental induction in man of sensitivity to leucine hypoglycemia. J Clin Invest 42(2):216–229
Felig P, Marliss E, Cahill GF Jr (1969) Plasma amino acid levels and insulin secretion in obesity. N Engl J Med 281(15):811–816
Freudenberg A, Petzke KJ, Klaus S (2012) Comparison of high-protein diets and leucine supplementation in the prevention of metabolic syndrome and related disorders in mice. J Nutr Biochem [Epub ahead of print]
Fulks RM, Li JB, Goldberg AL (1975) Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J Biol Chem 250(1):290–298
He W, Lam TK, Obici S, Rossetti L (2006) Molecular disruption of hypothalamic nutrient sensing induces obesity. Nat Neurosci 9(2):227–233
Izumi T, Kawamura K, Ueda H, Bungo T (2004) Central administration of leucine, but not isoleucine and valine, stimulates feeding behavior in neonatal chicks. Neurosci Lett 354(2):166–168
Keen-Rhinehart E, Bartness TJ (2008) Leptin inhibits food-deprivation-induced increases in food intake and food hoarding. Am J Physiol Regul Integr Comp Physiol 295(6):R1737–R1746
Klingenspor M, Niggemann H, Heldmaier G (2000) Modulation of leptin sensitivity by short photoperiod acclimation in the Djungarian hamster, Phodopus sungorus. J Comp Physiol B 170(1):37–43
Koch C, Augustine RA, Steger J, Ganjam GK, Benzler J, Pracht C et al (2010) Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity. J Neurosci 30(48):16180–16187
Lam TK, Schwartz GJ, Rossetti L (2005) Hypothalamic sensing of fatty acids. Nat Neurosci 8(5):579–584
Laviano A, Muscaritoli M, Cascino A, Preziosa I, Inui A, Mantovani G et al (2005) Branched-chain amino acids: the best compromise to achieve anabolism? Curr Opin Clin Nutr Metab Care 8(4):408–414
Mercer JG (1998) Regulation of appetite and body weight in seasonal mammals. Comp Biochem Physiol C: Pharmacol Toxicol Endocrinol 119(3):295–303
Mercer JG, Tups A (2003) Neuropeptides and anticipatory changes in behaviour and physiology: seasonal body weight regulation in the Siberian hamster. Eur J Pharmacol 480(1–3):43–50
Migrenne S, Magnan C, Cruciani-Guglielmacci C (2007) Fatty acid sensing and nervous control of energy homeostasis. Diabetes Metab 33(3):177–182
Morrison CD, Xi X, White CL, Ye J, Martin RJ (2007) Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism. Am J Physiol Endocrinol Metab 293(1):E165–E171
Nairizi A, She P, Vary TC, Lynch CJ (2009) Leucine supplementation of drinking water does not alter susceptibility to diet-induced obesity in mice. J Nutr 139(4):715–719
Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY et al (2007) Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449(7159):228–232
Pocai A, Lam TK, Obici S, Gutierrez-Juarez R, Muse ED, Arduini A et al (2006) Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats. J Clin Invest 116(4):1081–1091
Potier M, Darcel N, Tome D (2009) Protein, amino acids and the control of food intake. Curr Opin Clin Nutr Metab Care 12(1):54–58
Ropelle ER, Pauli JR, Fernandes MF, Rocco SA, Marin RM, Morari J et al (2008) A central role for neuronal AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in high-protein diet-induced weight loss. Diabetes 57(3):594–605
Rousseau K, Atcha Z, Cagampang FR, Le RP, Stirland JA, Ivanov TR et al (2002) Photoperiodic regulation of leptin resistance in the seasonally breeding Siberian hamster (Phodopus sungorus). Endocrinology 143(8):3083–3095
Tups A, Ellis C, Moar KM, Logie TJ, Adam CL, Mercer JG et al (2004) Photoperiodic regulation of leptin sensitivity in the Siberian hamster, Phodopus sungorus, is reflected in arcuate nucleus SOCS-3 (suppressor of cytokine signaling) gene expression. Endocrinology 145(3):1185–1193
Tups A, Stohr S, Helwig M, Barrett P, Krol E, Schachtner J et al (2012) Seasonal leptin resistance is associated with impaired signalling via JAK2-STAT3 but not ERK, possibly mediated by reduced hypothalamic GRB2 protein. J Comp Physiol B 182(4):553–567
Wijekoon EP, Skinner C, Brosnan ME, Brosnan JT (2004) Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Can J Physiol Pharmacol 82(7):506–514
Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH (2007) Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56(6):1647–1654
Acknowledgments
This study was funded by the German Ministry of Education and Research (Ref. No: 0315087, to AT).
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by G. Heldmaier.
Rights and permissions
About this article
Cite this article
Koch, C.E., Göddeke, S., Krüger, M. et al. Effect of central and peripheral leucine on energy metabolism in the Djungarian hamster (Phodopus sungorus). J Comp Physiol B 183, 261–268 (2013). https://doi.org/10.1007/s00360-012-0699-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00360-012-0699-y
Keywords
- Body weight regulation
- Food intake
- Hypothalamus
- Nutrient sensing