Abstract
Leptin is an important regulator of appetite and energy expenditure in mammals, but its role in fish metabolism control is poorly understood. Our previous studies demonstrated that leptin has an effect on the regulation of food intake and energy expenditure as well as lipid metabolism (stimulation of lipolysis and inhibition of adipogenesis) in the grass carp Ctenopharyngodon idella. To further investigate the role of leptin in fish, the effects of glucose, insulin and triiodothyroxine (T3) on the expression levels of leptin and leptin receptor (Lepr) and the effects of leptin on the activities of critical glucose metabolism enzymes in grass carp hepatocytes were evaluated in the present study. Our data indicated that leptin gene expression was induced by glucose in a dose-dependent manner, while Lepr gene expression exhibited a biphasic change. A high dose of insulin (100 ng/mL) significantly up-regulated the expression of leptin and Lepr. Leptin expression was markedly up-regulated by a low concentration of T3 but inhibited by a high concentration of T3. T3 up-regulated Lepr expression in a dose-dependent manner. Together, these data suggest that leptin had a close relationship with three factors (glucose, insulin and T3) and might participate in the regulation of glucose metabolism in grass carp. In addition, we also found that leptin affected the activities of key enzymes that are involved in glucose metabolism, which might be mediated by insulin receptor substrate-phosphoinositol 3-kinase signaling.
Similar content being viewed by others
Abbreviations
- G6Pase:
-
Glucose 6-phosphatase
- G6PD:
-
Glucose-6-phosphate dehydrogenase
- GK:
-
Glucokinase
- IRS-PI3K:
-
Insulin receptor substrate-phosphatidylinositol-3-OH-kinase
- JAK-STAT:
-
Janus kinase-signal transducer and activator of transcription
- Lepr:
-
Leptin receptor
- LPL:
-
Lipoprotein lipase
- ME:
-
Malic enzyme
- NPY:
-
Neuropeptide Y
- PEPCK:
-
Phosphoenolpyruvate carboxykinase
- PK:
-
Pyruvate kinase
- SCD1a:
-
Stearoyl-CoA desaturase 1a
- T3:
-
Triiodothyroxine
- UCP2:
-
Uncoupling protein 2
References
Aguilar AJ, Conde-Sieira M, Polakof S, Míguez JM, Soengas JL (2010) Central leptin treatment modulates brain glucosensing function and peripheral energy metabolism of rainbow trout. Peptides 31(6):1044–1054
Alegre M, Ciudad CJ, Fillat C, Guinovart JJ (1988) Determination of glucose-6-phosphatase activity using the glucose-dehydrogenase-coupled reaction. Anal Biochem 173(1):185–189
Aronoff SL, Berkowitz K, Shreiner B, Want L (2004) Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectr 17(3):183–190
Bentle LA, Lardy HA (1976) Interaction of anions and divalent metal ions with phosphoenolpyruvate carboxykinase. J Biol Chem 251(10):2916–2921
Bjørbæk C, Kahn BB (2004) Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res 59:305–331
Bossowski A, Sawicka B, Szalecki M, Koput A, Wysocka J, Zelazowska-Rutkowska B (2010) Analysis of serum adiponectin, resistin and leptin levels in children and adolescents with autoimmune thyroid disorders. J Pediatr Endocrinol Metab 23(4):369–377
Cabanelas A, Cordeiro A, Santos Almeida NA, Monteiro de Paula GS, Coelho VM, Ortiga-Carvalho TM, Pazos-Moura CC (2010) Effect of triiodothyronine on adiponectin expression and leptin release by white adipose tissue of normal rats. Horm Metab Res 42(4):254–260
Chinookoswong N, Wang JL, Shi ZQ (1999) Leptin restores euglycemia and normalizes glucose turnover in insulin deficient diabetes in the rat. Diabetes 48(7):1487–1492
Copeland DL, Duff RJ, Liu Q, Prokop J, Londraville RL (2011) Leptin in teleost fishes: an argument for comparative study. Front Physiol 2:26
Dagogo-Jack S, Tykodi G, Umamaheswaran I (2005) Inhibition of cortisol biosynthesis decreases circulating leptin levels in obese humans. J Clin Endocrinol Metab 90(9):5333–5335
Denroche HC, Levi J, Wideman RD, Sequeira RM, Huynh FK, Covey SD, Kieffer TJ (2011) Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling. Diabetes 60(5):1414–1423
Denroche HC, Huynh FK, Kieffer TJ (2012) The role of leptin in glucose homeostasis. J Diabetes Investig 3(2):115–129
Escobar-Morreale HF, Escobar del Rey F, Morreale de Escobar G (1997) Thyroid hormones influence serum leptin concentrations in the rat. Endocrinology 138:4485–4488
Farasat T, Cheema AM, Khan MN (2012) Hyperinsulinemia and insulin resistance is associated with low T(3)/T(4) ratio in prediabetic euthyroid Pakistani subjects. J Diabetes Complications 26(6):522–525
Flores-Morales A, Greenhalgh CJ, Norstedt G, Rico-Bautista E (2006) Negative regulation of growth hormone receptor signaling. Mol Endocrinol 20(2):241–253
Friedman JM (2009) Leptin at 14y of age: an ongoing story. Am J Clin Nutr 89(3):973S–979S
Ghilardi N, Skoda RC (1997) The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line. Mol Endocrinol 11:393–399
Havel PJ, Uriu-Hare JY, Liu T, Stanhope KL, Sern JS, Keen CL, Ahren AB (1998) Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin. Am J Physiol Regul Integr Comp Physiol 274(5 Pt 2):R1482–R1491
He S, Liang XF, Li L, Huang W, Shen D, Tao YX (2013) Gene structure and expression of leptin in Chinese perch. Gen Comp Endocrinol 194:183–188
Henly DC, Hoffmann NV, Galligan PA, Morris P (1999) Inhibitory effects of leptin on glucokinase and glycolysis in primary rat hepaotocytes. Diabetes towards 2000: abstract book: the 4th international diabetes federation. Western Pacific Region, Congress, Sydney, pp 25–28
Hollenberg AN, Forrest D (2008) The thyroid and metabolism: the action continues. Cell Metab 8(1):10–12
Huising MO, Geven EJ, Kruiswijk CP, Nabuurs SB, Stolte EH, Spanings FA, Verburg-van Kemenade BM, Flik G (2006) Increased leptin expression in common Carp (Cyprinus carpio) after food intake but not after fasting or feeding to satiation. Endocrinology 147(12):5786–5797
Hulbert AJ (2000) Thyroid hormones and their effects: a new perspective. Biol Rev Camb Philos Soc 75(4):519–631
Kapadia KB, Bhatt PA, Shah JS (2012) Association between altered thyroid state and insulin resistance. J Pharmacol Pharmacother 3(2):156–160
Kelesidis T, Kelesidis I, Chou S, Mantzoros CS (2010) Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 52(2):93–100
Lafrance V, Wataru Inoue W, Kana B, Luhesh GN (2010) Leptin modulates cell morphology and cytokine release in microglia. Brain Behav Immun 24(3):358–365
Li GG, Liang XF, Xie Q, Li GZ, Yu Y, Lai K (2010) Gene structure, recombinant expression and functional characterization of grass carp leptin. Gen Comp Endocrinol 166(1):117–127
Lin CY, Higginbotham DA, Judd RL, White BD (2002) Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 282(5):E1084–E1091
Liu L, Karkanias GB, Morales JC, Hawkins M, Barzilai N, Wang J, Rossetti L (1998) Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes. J Biol Chem 273(47):31160–31167
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408
Lu RH, Liang XF, Wang M, Zhou Y, Bai XL, He Y (2012) The role of leptin in lipid metabolism in fatty degenerated hepatocytes of the grass carp Ctenopharyngodon idellus. Fish Physiol Biochem 38(6):1759–1774
Luvizotto RAM, Conde SJ, Sibio MT, Nascimento AF, Lima-Leopoldo AP, Leopoldo AS, Padovani CR, Cicogna AC, Nogueira CR (2010) Administration of physiologic levels of triiodothyronine increases leptin expression in calorie-restricted obese rats, but does not influence weight loss. Metabolism 59(1):1–6
Luvizotto RAM, Sibio MT, Olimpio RMC, Nascimento AF, Lima-Leopoldo AP, Leopoldo AS, Padovani CR, Cicogna AC, Nogueira CR (2011) Supraphysiological triiodothyronine doses diminish leptin and adiponectin gene expression, but do not alter resistin expression in calorie restricted obese rats. Horm Metab Res 43(7):452–457
Medina-Gomez G, Calvo RM, Obregon MJ (2004) T3 and Triac inhibit leptin secretion and expression in brown and white rat adipocytes. Biochim Biophys Acta 1682(1–3):38–47
Mitchell SE, Ruben N, Morris A, Tovar S, Grant C, Cruickshank M, Rayner DV, Dieguez C, Williams LM (2009) Leptin receptor gene expression and number in the brain are regulated by leptin level and nutritional status. J Physiol 587(14):3573–3585
Monteverdi GH, Di Giulio RT (2000) Vitellogenin association and oocytic accumulation of thyroxine and 3,5,30-triiodothyronine in gravid Fundulus heteroclitus. Gen Comp Endocrinol 120(2):198–211
Moreno M, de Lange P, Lombardi A, Silvestri E, Goglia F (2008) Metabolic effects of thyroid hormone derivatives. Thyroid 18(2):239–253
Moreno-Aliaga MJ, Stanhope KL, Gregoire FM, Warden CH, Havel PJ (2003) Effects of inhibiting transcription and protein synthesis on basal and insulin-stimulated leptin gene expression and leptin secretion in cultured rat adipocytes. Biochem Biophys Res Commun 307(4):907–914
Morton GJ, Schwartz MW (2011) Leptin and the CNS control of glucose metabolism. Physiol Rev 91(2):389–411
Morton GJ, Gelling RW, Niswender KD, Morrison CD, Kim F, Schwartz MW (2005) Leptin signaling in the hypothalamic arcuate nucleus is a key determinant of glucose tolerance and hepatic insulin action. Obes Res 13(1):198–201
Panserat S, Médale F, Blin C, Brèque J, Vachot C, Plagnes-Juan E, Gomes E, Krishnamoorthy R, Kaushik S (2000) Hepaticglucokinase is induced by dietary carbohydrates in rainbow trout (Oncorhynchus mykiss), common carp (Cyprinus carpio) and gilthead seabream (Sparus aurata). Am J Physiol 278(5):R1164–R1170
Pocai A, Morgan K, Buettner C, Gutierrez-Juarez R, Obici S, Rossetti L (2005) Central leptin acutely reverses diet-induced hepatic insulin resistance. Diabetes 54(11):3182–3189
Power DM, Llewellyn L, Faustino M, Nowell MA, Bjornsson BT, Einarsdottir IE, Canario AV, Sweeney GE (2001) Thyroid hormones in growth and development of fish. Comp Biochem Physiol C 130(4):447–459
Rønnestad I, Nilsen TO, Murashita K, Angotzi AR, Moen AGG, Stefansson SO, Kling P, Bjornsson BT, Kurokawa T, Ronnestad I (2010) Leptin and leptin receptor genes in Atlantic salmon: cloning, phylogeny, tissue distribution and expression correlated to long-term feeding status. Gen Comp Endocrinol 168(1):55–70
Rossetti L, Massillon D, Barzilai N, Vuguin P, Chen W, Hawkins M, Wu J, Wang J (1997) Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J Biol Chem 272(44):27758–27763
Schulz LC, Widmaier EP (2007) Leptin receptor. In: Castracane VD, Henson MC (eds) Leptin. Springer Science & Business Media Inc, New York, pp 11–31
Sesmilo G, Casamitjana R, Halperin I, Gomis R, Vilardell E (1998) Role of thyroid hormones on serum leptin levels. Eur J Endocrinol 139(4):428–430
Shankaran H, Wiley HS, Resat H (2007) Receptor downregulation and desensitization enhance the information processing ability of signalling receptors. BMC Syst Biol 1:48–62
Steppan CM, Crawford TD, Chidsey-Frink KL, Ke H, Swick AG (2000) Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 92(1–3):73–78
Su Q, Mumick S, Nizner P, Tota MR, Menetski J, Reitman ML, Macneil DJ (2008) Deficiency in cytosolic malic enzyme does not increase acetaminophen-induced hepato-toxicity. Basic Clin Pharmacol Toxicol 103(1):36–42
Swoap SJ (2008) The pharmacology and molecular mechanisms underlying temperature regulation and torpor. Biochem Pharmacol 76(7):817–824
Terrien X, Prunet P (2013) Crossregulation of the thyroid hormone and corticosteroids in amphibians and fish: The effects of endocrine disruption. doi:10.5772/54314
Tranulis MA, Dregni O, Christophersen B, Krogdahl A, Borrebaek B (1996) A glucokinase-like enzyme in the liver of Atlantic salmon (Salmo salar). Comp Biochem Physiol B 114(1):35–39
Walker CG, Bryson JM, Bell-Anderson KS, Hancock DP, Denyer GS, Caterson ID (2005) Insulin determines leptin responses during a glucose challenge in fed and fasted rats. Int J Obes 29(4):398–405
Wendy MM, Francine MG, Kimber LS, Charles VM, Tooru MM, Craig HW, Judith SS, Peter JH (1998) Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology 139(2):551–558
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432
Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (31172420, 31072219, 31402311), the National Basic Research Program of China (2014CB138601), the China Postdoctoral Science Foundation (52201-12971, 2013M531708). We thank Dr. Ya-Xiong Tao (Auburn University, Auburn, Alabama, USA) for extensive editing of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Additional information
Yi Zhou and Rong-Hua Lu contributed equally to this work.
Rights and permissions
About this article
Cite this article
Lu, RH., Zhou, Y., Yuan, XC. et al. Effects of glucose, insulin and triiodothyroxine on leptin and leptin receptor expression and the effects of leptin on activities of enzymes related to glucose metabolism in grass carp (Ctenopharyngodon idella) hepatocytes. Fish Physiol Biochem 41, 981–989 (2015). https://doi.org/10.1007/s10695-015-0063-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10695-015-0063-8