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Horm Metab Res 2002; 34(7): 400-405
DOI: 10.1055/s-2002-33473
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Leptin Treatment during the Neonatal Period is Associated with Higher Food Intake and Adult Body Weight in Rats

C.  de Oliveira Cravo 1 , C.  V.  Teixeira1 , M.  C. F.  Passos 2 , S.  C. P.  Dutra 1 , E.  G.  de Moura 1 , C.  Ramos 1
  • 1Department of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Brazil
  • 2Department of Applied Nutrition, Nutrition Institute, State University of Rio de Janeiro, Brazil
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Publication History

Received: 24 September 2001

Accepted after revision: 4 February 2002

Publication Date:
21 August 2002 (online)

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Abstract

For this study, we have determined the effects of neonatal leptin treatment on the evolution of body weight. Experiment 1: pups were divided into two groups: LepF - injected with leptin (8 µg/100 g of body weight) for the first 10 days of lactation and control (C) - receiving saline. Experiment 2: pups were divided into two groups: LepL - injected with the same leptin concentration of experiment one for the last 10 days of lactation, and C, which received saline. Body weight and food intake were monitored until age 150 days, after which leptin concentrations were measured by ELISA. The LepF group had a significant increase in body weight (p < 0.05) from day 98 onward, in food intake (p < 0.05) from day 74 onward, and higher serum leptin concentration compared to the control (108 %, p < 0.05). The LepL group had a significant increase in body weight (p < 0.05) from day 113 onward, in food intake from day 121 onward (p < 0.001), and higher serum leptin concentration compared to controls (6.9 %, p < 0.05). These results suggest that both periods of lactation constituted a critical window for body weight and food intake programming, but the effects are more marked when the leptin is injected within the first ten days.

Key words

Neonatal - Leptin - Body Weight - Food Intake - Rats

References

  • 1 Schwartz M W, Seeley R J, Campfield L A, Burn P, Baskin D G. Identification of targets of leptin action in rat hypothalamus.  J Clin Invest. 1996;  98 (5) 1101-1106
    CrossrefPubMedGoogle Scholar
  • 2 Pelleymounter M A, Cullen M J, Baker M B, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice.  Science. 1995;  269 540-543
    CrossrefPubMedGoogle Scholar
  • 3 Campfield L A, Smith F J, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks.  Science. 1995;  269 546-549
    CrossrefPubMedGoogle Scholar
  • 4 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.  Nature. 1998;  395 763-770
    CrossrefPubMedGoogle Scholar
  • 5 Barraclough C A, Gorski R A. Evidence that the hypothalamus is responsible for androgen-induced sterility in the female rat.  Endocrinology. 1961;  68 68-79
    PubMedGoogle Scholar
  • 6 vom Saal F S, Bronson F H. Sexual characteristics of adult female mice are correlated with their blood testosterone levels during prenatal development.  Science. 1980;  208 597-599
    PubMedGoogle Scholar
  • 7 Edwards C RW, Benedidtsson R, Lindsay R S, Seckl J R. Dysfunction of placental glucocorticoid barrier: Link between fetal environment and adult hypertension?.  Lancet. 1993;  341 355-357
    CrossrefPubMedGoogle Scholar
  • 8 Catalani A, Casolini P, Scaccianoce S, Patacchioli F R, Spinozzi P, Angelucci L. Maternal corticosterone during lactation permanently affects brain corticosteroid receptors, stress response and behaviour in rat progeny.  Neuroscience. 2000;  100 319-325
    CrossrefPubMedGoogle Scholar
  • 9 Walker P, Courtin F. Transient neonatal hyperthyroidism results in hypothyroidism in the adult rat.  Endocrinology. 1985;  116 2246-2250
    CrossrefPubMedGoogle Scholar
  • 10 Pracyck J B, Seidler F J, McCook E C, Slotkin T A. Pituitary-thyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: Ontogeny of regulation and long term programming of responses.  J Dev Physiol. 1992;  18 105-109
    PubMedGoogle Scholar
  • 11 Dorner G, Plagemann A. Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life.  Horm Metab Res. 1994;  26 (5) 213-221
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Passos M CF, Ramos C F, Moura E G. Short and long term effects of malnutrition in rats during lactation on the body weight of offspring.  Nutr Res. 2000;  20 (11) 1603-1612
    CrossrefPubMedGoogle Scholar
  • 13 Mistry A M, Swick A, Romsos D R. Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice.  American Journal Physiology. 1999;  46 R742-R747
    PubMedGoogle Scholar
  • 14 Ahima R S, Prabakaran D, Flier J S. Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding.  The Journal of Clinical Investigation. 1998;  101 (5) 1020-1027
    CrossrefPubMedGoogle Scholar
  • 15 Butte N F, Hopkinson J M, Nicolson M A. Leptin in human reproduction: Serum leptin levels in pregnant and lactating women.  J Clin Endocrinol Metab. 1997;  82 585-589
    CrossrefPubMedGoogle Scholar
  • 16 McGuire M K, Beerman K, McGuire M A, Shafii B, Houseknecht K. Relationships among human milk and plasma leptin concentrations and simple anthropometric measurements in lactating humans.  Nutrition Research. 2000;  20 (12) 1697-1706
    CrossrefPubMedGoogle Scholar
  • 17 Rayner D V, Dalgliesh G D, Duncan J S, Hardie L J, Hoggard N, Trayhurn P. Postnatal development of the ob gene system: elevated leptin levels in suckling fa/fa rats.  American Journal Physiology. 1997;  273 R446-R450
    PubMedGoogle Scholar
  • 18 Bayne K. Revised Guide for the Care and Use of Laboratory Animals available.  Am Phys Soc Physiol. 1996;  39 (4) 208-211
    PubMedGoogle Scholar
  • 19 Malendowicz L K, Macchi C, Nussdorfer G G, Nowak K W. Acute effects of recombinant murine leptin on rat pituitary-adrenocortical function.  Endocrine Research. 1998;  24 (2) 235-246
    PubMedGoogle Scholar
  • 20 Yuan C S, Attle A S, Zhang L, Lynch J P, Xie J T, Shi Z Q. Leptin reduces body weight gain in neonatal rats.  Pediatric Research. 2000;  48 (3) 380-383
    PubMedGoogle Scholar
  • 21 Prouxl K, Clavel S, Nault G, Richard D, Walker C D. High neonatal leptin exposure enhances brain GR expression and feedback efficacy on the adrenocortical axis of developing rats.  Endocrinology. 2001;  142 (11) 4607-4616
    CrossrefPubMedGoogle Scholar
  • 22 Lucas A. Early Nutrition and later outcome. In: Ziegler EE, Lucas A, Moro GE (eds) Nutrition of the very low birthweight infant. Nestlé Nutrition Workshop Series. Philadelphia, Pennsylvania; Vevey/Lippincott, Williams & Wilkins 1999 43: 1-13
    Google Scholar
  • 23 Lucas A. Programming by early nutrition in man. In: CIBA Foundation Symposium The childhood environment and adult disease. Chichester; John Wiley 1991 156: 38-55
    Google Scholar
  • 24 Lucas A. Role of nutritional programming in determining adult morbidity.  Arch Dis Child. 1994;  71 288-290
    CrossrefPubMedGoogle Scholar
  • 25 Waterland R A, Garza C. Potencial mechanisms of metabolic imprinting that lead to chronic disease.  Am J Clin Nutr. 1999;  69 179-197
    PubMedGoogle Scholar
  • 26 Oates M, Noodside B, Walker C D. Chronic leptin administration in developing rats reduces stress responsiveness partly through changes in maternal behavior.  Hormones and Behavior. 2000;  37 366-376
    CrossrefPubMedGoogle Scholar
  • 27 Tanidaa M, Iwashitaa S, Ootsukab Y, Teruib N, Suzukia M. Leptin injection into white adipose tissue elevates renal sympathetic nerve activity dose-dependently through the afferent nerves pathway in rats.  Neuroscience Letters. 2000;  293 107-110
    CrossrefPubMedGoogle Scholar
  • 28 Passos M CF, Ramos C F, Dutra S CP, Mouço T, Moura E G. Long-term effects of malnutrition during lactation on the thyroid function of offspring.  Horm Metab Res. 2002;  34 40-43
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Casabiel X, Piñero V, Tomé M, Peinó R, Diéguez C, Casanueva F F. Presence of leptin in colostrum and/or breast milk of neonatal food intake.  J Clin Endocr Metab. 1997;  82 4270-4273
    CrossrefPubMedGoogle Scholar
  • 30 Houseknecht K L, McGuire M K, Portocarrero C P, McGuire M A, Beerman K. Leptin is present in human milk; relationship with maternal leptin concentrations and adiposity.  Biochem Biophys Res Commun. 1997;  240 742-747
    CrossrefPubMedGoogle Scholar
  • 31 Herrera E, Lasuncion M A, Huerta L, Martin-Hidalgo A. Plasma leptin levels in rat mother and offspring during pregnancy and lactation.  Biology of the Neonate. 2000;  78 315-320
    CrossrefPubMedGoogle Scholar
  • 32 Qiu J, Ogus S, Lu R, Chehab F F. Transgenic mice orespressing leptin accumulate adipose mass at an older, but not younger age.  Endocrinology. 2001;  142 (1) 348-358
    CrossrefPubMedGoogle Scholar
  • 33 Ahima R S, Hileman S M. Postnatal regulation of hypothalamic neuropeptide expression by leptin: Implifications for energy balance and body weight regulation.  Regulatory Peptides. 2000;  92 1-7
    CrossrefPubMedGoogle Scholar
  • 34 Barker D J. The fetal and infant origins of disease.  Eur J Clin Invest. 1995;  25 457-463
    CrossrefPubMedGoogle Scholar
  • 35 Nagy S U, Csaba G. Dose dependence of the thyrotropin (TSH) receptor damaging effect of gonadotropin in the newborn rats.  Acta Phys Acad Scient Hung. 1980;  56 417-420
    PubMedGoogle Scholar
  • 36 Csaba G, Török O. Influence of insulin and biogenic amines on the division of Ghang liver cells after primary exposure (imprinting) and repeated treatments.  Cytobios. 1991;  66 153-156
    PubMedGoogle Scholar
  • 37 McIntosh J, Anisman H, Merali Z. Short- and long-periods of neonatal maternal separation differentially affect anxiety and feeding in adult rats: Gender-dependent effects.  Developmental Brain Research. 1999;  113 (1 - 2) 97-106
    CrossrefPubMedGoogle Scholar
  • 38 Weaver S A, Aherne F X, Meaney M J, Schaefer A L, Dixon W T. Neonatal handling permanently alters hypothalamic-pituitary-adrenal axis function, behaviour, and body weight in boars.  Journal of Endocrinology. 2000;  164 (3) 349-359
    CrossrefPubMedGoogle Scholar
  • 39 Penke Z, Felszeghy K, Fernette B, Sage D, Nyakas C, Burlet A. Postnatal maternal deprivation produces long-lasting modifications of the stress response, feeding and stress-related behaviour in the rat.  The European Journal of Neuroscience. 2001;  14 (4) 747-755
    PubMedGoogle Scholar
  • 40 Calvo R, Obregon M J, Ruiz de Ona C, Escobar del Ray F, Morreale de Escobar G. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3’-triiodothyronine in the protection of the fetal brain.  J Clin Invest. 1990;  86 (3) 889-899
    PubMedGoogle Scholar

Dr. E. G. de Moura

Departamento de Ciências Fisiológicas, 5° andar · Instituto de Biologia · Universidade do Estado do Rio de Janeiro

Av. 28 de setembro 87 · Rio de Janeiro RJ, 20550-030 · Brazil ·

Phone: + 55 (21) 25 87 61 34

Fax: + 55 (21) 25 87 61 29

Email: egmoura@uerj.br