Exp Clin Endocrinol Diabetes 2015; 123(07): 398-404
DOI: 10.1055/s-0035-1549936
Article
© Georg Thieme Verlag KG Stuttgart · New York

Serum Leptin in Neonatal Lambs is Associated with Temperature, Plasma Lipids and Metabolites

J. Schilling
1   LWL-University Klinik Hamm, Hamm, Germany
,
R. Hospes
2   Gynaecology and Andrology in Small and Large Animals, Department of Obstetrics, University Veterinary Medicine Hospital, Giessen, Germany
,
G. Kaya
2   Gynaecology and Andrology in Small and Large Animals, Department of Obstetrics, University Veterinary Medicine Hospital, Giessen, Germany
,
K. Failing
3   Department of Biomathematics and Data Processing, University Veterinary Medicine Hospital, Giessen, Germany
,
L. Gortner
4   University Children’s Hospital, Homburg/Saar, Germany
,
S. A. Wudy
5   Center of Child and Adolescent Medicine, Justus Liebig University, Peptide Hormone Research Unit, Laboratory for Translational Hormone Analytics in Pediatric Endocrinology, Giessen, Germany
,
W. F. Blum
5   Center of Child and Adolescent Medicine, Justus Liebig University, Peptide Hormone Research Unit, Laboratory for Translational Hormone Analytics in Pediatric Endocrinology, Giessen, Germany
› Author Affiliations
Further Information

Publication History

received 25 January 2015
first decision 11 April 2015

accepted 17 April 2015

Publication Date:
26 May 2015 (online)

Abstract

In this study we investigated changes of serum leptin in 74 newborn lambs and associations with environmental temperature (from − 8°C to + 25°C), body temperature, and concentrations of plasma lipids, 3-beta-hydroxybutyric acid and blood glucose. A leptin radioimmunoassay was established, using an antiserum (rabbit) produced against a partial sequence of ovine leptin (31–44). Before measurement, serum samples were denatured. The sensitivity of the assay was 0.4 µg l−1 and intra- and interassay coefficients of variation were 5.1% and 2.5%, respectively. Blood samples were collected immediately after birth up to 24 h postnatally (pn). Median leptin concentrations at birth and 24 h pn were 20.9 and 52.7 µg l−1, respectively. Because of non-normal distribution, leptin concentrations were converted to log(leptin) before further statistical processing. The change in log(leptin) during the first 24 h was highly significant (p<0.0001). Correlation analysis showed significant associations between serum leptin and the following variables: environmental temperature 24 h pn (r=0.34, p<0.005), log(plasma triglycerides) 24 h pn (r=0.50, p<0.001), log(plasma 3-beta-hydroxybutyric acid) 24 h pn (r=−0.50, p<0.001), blood glucose 6 h pn (r=0.43, p<0.001) and plasma cholesterol 12 h pn (r=0.38, p=0.001). We conclude that this radioimmunoassay is suited to measure total serum ovine leptin and that total leptin is already regulated in the very early postnatal phase. Leptin is increased at higher environmental temperatures, consistent with leptin’s suppressive effect on energy expenditure and appetite. Furthermore, leptin levels are associated with plasma concentrations of lipids and lipid metabolites.

 
  • References

  • 1 Zhang Y, Proenca R, Maffei M et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432
  • 2 Blum WF, Englaro P, Heiman M et al. Clinical Studies of Serum Leptin. In: Blum WF, Kiess W, Rascher W. (eds.) Leptin The Voice of Adipose Tissue. Heidelberg, Leipzig: J.A. Barth Verlag; 1997: 201-218
  • 3 Amitani M, Asakawa A, Amitani H et al. The role of leptin in the control of insulin-glucose axis. Front Neurosci 2013; 7: 51
  • 4 Cinti S, Frederich RC, Zingaretti MC et al. Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue. Endocrinology 1997; 138: 797-804
  • 5 Zamorano PL, Mahesh VB, De Sevilla LM et al. Expression and localization of the leptin receptor in endocrine and neuroendocrine tissues of the rat. Neuroendocrinology 1997; 65: 223-228
  • 6 Mizuno T, Bergen H, Kleopoulos S et al. Effects of nutritional status and aging on leptin gene expression in mice: importance of glucose. Horm Metab Res 1996; 28: 679-684
  • 7 Kamohara S, Burcelin R, Halaas JL et al. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 1997; 389: 374-377
  • 8 Herrera E, Lasuncion MA, Huerta L et al. Plasma leptin levels in rat mother and offspring during pregnancy and lactation. Biol Neonate 2000; 78: 315-320
  • 9 McFadin EL, Morrison CD, Buff PR et al. Leptin concentrations in periparturient ewes and their subsequent offspring. J Anim Sci 2002; 80: 738-743
  • 10 Schubring C, Siebler T, Kratzsch J et al. Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight. Clin Endocrinol (Oxf) 1999; 51: 199-204
  • 11 Eales FA, Small J, Gilmour JS. Neonatal mortality of lambs and its causes. Moredun Research Institute 1983; 289-298
  • 12 Altschul SF, Madden TL, Schaffer AA et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25: 3389-3402
  • 13 Hossenlopp P, Seurin D, Segovia-Quinson B et al. Analysis of serum insulin-like growth factor binding proteins using Western blotting: Use of the method for titration of the binding proteins and competitive binding studies. Analytical Biochemistry 1986; 154: 138-143
  • 14 Blum WF, Breier BH. Radioimmunoassays for IGFs and IGFBPs. Growth Regulation 1994; 4 (Suppl. 01) 11-19
  • 15 Wahlefeld AW. Triglycerid-Bestimmung nach enzymatischer Verseifung. In: Bergmeyer HU. (ed) Methoden der enzymatischen Analyse. 3rd edition Weinheim: Verlag Chemie; 1974: 1871-1878
  • 16 Siedel HS, Schlumberger S, Klose J et al. Improved reagent for the enzymatic determination of serum cholesterol. J Clin Chem Clin Biochem 1981; 19: 838-839
  • 17 Williamson DH, Mellanby J, Krebs HA. Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J 1962; 82: 90-96
  • 18 Delavaud C, Bocquier F, Chilliard Y et al. Plasma leptin determination in ruminants: effect of nutritional status and body fatness on plasma leptin concentration assessed by a specific RIA in sheep. J Endocrinol 2000; 165: 519-526
  • 19 Bispham J, Budge H, Mostyn A et al. Ambient temperature, maternal dexamethasone, and postnatal ontogeny of leptin in the neonatal lamb. Pediatr Res 2002; 52: 85-90
  • 20 Schubring C, Kiess W, Englaro P et al. Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight. J Clin Endocrinol Metab 1997; 82: 1480-3
  • 21 Hytinantti T, Koistinen HA, Koivisto VA et al. Changes in leptin concentration during the early postnatal period: adjustment to extrauterine life?. Pediatr Res 1999; 45: 197-201
  • 22 Ehrhardt RA, Slepetis RM, Siegal-Willott J et al. Development of a specific radioimmunoassay to measure physiological changes of circulating leptin in cattle and sheep. J Endocrinol 2000; 166: 519-528
  • 23 Sinha MK, Opentanova I, Ohannesian JP et al. Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest 1996; 98: 1277-1282
  • 24 Lammert A, Kiess W, Bottner A et al. Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun 2001; 283: 982-988
  • 25 Peelman F, Van Beneden K, Zabeau L et al. Mapping of the leptin binding sites and design of a leptin antagonist. J Biol Chem 2004; 279: 41038-41046
  • 26 Houseknecht KL, Mantzoros CS, Kuliawat R et al. Evidence for leptin binding to proteins in serum of rodents and humans: modulation with obesity. Diabetes 1996; 45: 1638-1643
  • 27 Kiess W, Siebler T, Englaro P et al. Leptin as a metabolic regulator during fetal and neonatal life and in childhood and adolescence. J Pediatr Endocrinol Metab 1998; 11: 483-496
  • 28 Stoll-Becker S, Kreuder J, Reiss I et al. Influence of gestational age and intrauterine growth on leptin concentrations in venous cord blood of human newborns. Klin Padiatr 2003; 215: 3-8
  • 29 Grisaru-Granovsky S, Eitan R, Algur N et al. Maternal and umbilical cord serum leptin concentrations in small-for-gestational-age and in appropriate-for-gestational-age neonates: a maternal, fetal, or placental contribution?. Biol Neonate 2003; 84: 67-72
  • 30 Ehrhardt RA, Greenwood PL, Bell AW et al. Plasma leptin is regulated predominantly by nutrition in preruminant lambs. J Nutr 2003; 133: 4196-4201
  • 31 Alexander G. Quantitative development of adipose tissue in foetal sheep. Aust J Biol Sci 1978; 31: 489-503
  • 32 Yuen BS, Owens PC, McFarlane JR et al. Circulating leptin concentrations are positively related to leptin messenger RNA expression in the adipose tissue of fetal sheep in the pregnant ewe fed at or below maintenance energy requirements during late gestation. Biol Reprod 2002; 67: 911-916
  • 33 Ertl T, Funke S, Sarkany I et al. Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone. Biol Neonate 1999; 75: 167-176
  • 34 Onal EE, Uysal FK, Cinaz P et al. Serum leptin levels in twins and singleton newborns. J Pediatr Endocrinol Metab 2003; 16: 733-739
  • 35 Trayhurn P, Duncan JS, Rayner DV. Acute cold-induced suppression of ob (obese) gene expression in white adipose tissue of mice: mediation by the sympathetic system. Biochem J 1995; 311 (Pt 3) 729-733
  • 36 Hardie LJ, Rayner DV, Holmes S et al. Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem Biophys Res Commun 1996; 223: 660-665
  • 37 Ricci MR, Fried SK, Mittleman KD. Acute cold exposure decreases plasma leptin in women. Metabolism 2000; 49: 421-423
  • 38 Evans BA, Agar L, Summers RJ. The role of the sympathetic nervous system in the regulation of leptin synthesis in C57BL/6 mice. FEBS 1999; 444: 149-154
  • 39 Blumberg MS, Deaver K, Kirby RF. Leptin disinhibits nonshivering thermogenesis in infants after maternal separation. Am J Physiol 1999; 276: R606-R610
  • 40 Behrens H In: Behrens H. (ed.). Lehrbuch der Schafkrankheiten. 3rd ed Berlin und Hamburg: Parey; 1987
  • 41 Simon C, Gronfier C, Schlienger JL et al. Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: relationship to sleep and body temperature. J Clin Endocrinol Metab 1998; 83: 1893-1899
  • 42 Clarke IJ, Henry BA. Targeting energy expenditure in muscle as a means of combating obesity. Clin Exp Pharmacol Physiol 2010; 37: 121-124
  • 43 Altmann M, Sauerwein H, von Borell E. The relationships between leptin concentrations and body fat reserves in lambs are reduced by short-term fasting. J Anim Physiol Anim Nutr (Berl) 2006; 90: 407-413
  • 44 Wetzler S, Jean-Joseph G, Even P et al. Acute third ventricular administration of leptin decreases protein and fat in self-selecting rats. Behav Brain Res 2005; 159: 119-125
  • 45 Jequier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002; 967: 379-388
  • 46 Wabitsch M, Jensen PB, Blum WF et al. Insulin and cortisol promote leptin production in cultured human fat cells. Diabetes 1996; 45: 1435-1438
  • 47 Barr VA, Malide D, Zarnowski MJ et al. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology 1997; 138: 4463-4472
  • 48 Auwerx J, Staels B. Leptin. Lancet 1998; 351: 737-742
  • 49 Kalaivanisailaja J, Manju V, Nalini N. Lipid profile in mice fed a high-fat diet after exogenous leptin administration. Pol J Pharmacol 2003; 55: 763-769
  • 50 Kavazarakis E, Moustaki M, Gourgiotis D et al. Relation of serum leptin levels to lipid profile in healthy children. Metabolism 2001; 50: 1091-1094
  • 51 Meyer H, Kamphues J. Grundlagen der Ernährung von Neugeborenen. In: Walser K, Bostedt H. (eds.). Neugeborenen und Säuglingskunde der Tiere. Stuttgart: Ferdinand Enke Verlag; 1990. 55-61. 67-71
  • 52 Wang MY, Lee Y, Unger RH. Novel form of lipolysis induced by leptin. J Biol Chem 1999; 274: 17541-17544
  • 53 Deng C, Moinat M, Curtis L et al. Effects of beta-adrenoceptor subtype stimulation on obese gene messenger ribonucleic acid and on leptin secretion in mouse brown adipocytes differentiated in culture. Endocrinology 1997; 138: 548-552
  • 54 Sinha MK. Human leptin: the hormone of adipose tissue. Eur J Endocrinol 1997; 136: 461-464
  • 55 Iossa S, Lionetti L, Mollica MP et al. Effect of cold exposure on energy balance and liver respiratory capacity in post-weaning rats fed a high-fat diet. Br J Nutr 2001; 85: 89-96
  • 56 Shimabukuro M, Koyama K, Chen G et al. Direct antidiabetic effect of leptin through triglyceride depletion of tissues. Proc Natl Acad Sci USA 1997; 94: 4637-4641
  • 57 Banks WA, Coon AB, Robinson SM et al. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 2004; 53: 1253-1260