Advertisement

Regulation of Body Weight Homeostasis During Pregnancy and Lactation

  • M. C. García
  • R. M. Señaris
  • J. E. Caminos
  • M. Lopez
  • R. Nogueiras
  • O. Gualillo
  • F. Casanueva
  • C. Diéguez
Conference paper
Part of the Research and Perspectives in Endocrine Interactions book series (RPEI)

Summary

Pregnancy is a hypermetabolic state in which a great increase in maternal body fat and weight occurs, mostly in the final trimester of gestation, and it is associated with relevant neuroendocrine changes as adaptations to the new hormonal status. Data gleaned over the last few years have allowed the characterization of different central and peripheral signals involved in the regulation of body weight homeostasis.

Serum leptin levels were significantly increased during rat gestation. Leptin mRNA levels in both the adipose tissue and placenta were higher as pregnancy progressed, suggesting a role for both tissues in the hyperproduction of leptin. This paradoxical increase in leptin concentration during gestation suggests that a physiological state of leptin resistance may exist at the hypothalamic level that may explain the hyperphagia observed in pregnant rats. A specific reduction of the mRNA levels encoding the leptin receptor isoform Ob-Rb in the hypothalamus of pregnant rats in comparison to non-pregnant animals suggests that, during pregnancy, the hypothalamus shows a physiological resistance to the high levels of leptin due, at least in part, to a decrease in the expression of the long, biologically active form of the leptin receptor (Ob-Rb). During lactation an increased expression of some of the short forms of the leptin receptor (Ob-Re and Ob-Rf) was found. This increase could contribute to the hyperphagia present during lactation. Finally, Neuropeptide (NPY)mRNA levels in the arcuate nucleus were increased during pregnancy and lactation whereas melanin-concentrating hormone (MCH) and preprorexin levels were decreased. Therefore, it is possible that NPY could also be one of the adaptive mechanisms that take place during pregnancy and lactation in order to meet increased metabolic requirements.

Keywords

Arcuate Nucleus Increase Food Intake Orexin Receptor Hypothalamic Level Body Weight Homeostasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amico JA, Thomas A, Crowley RS, Burmeister LA (1998) Concentrations of leptin in the serum of pregnant, lactating, and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue. Life Sci 63:1387–1395.PubMedCrossRefGoogle Scholar
  2. Aqua MS, Rizzu P, Lindsay EA, Shafer LG, Zackai EH, Overhauser J, Baldini A (1995) Duplication of 3q syndrome: molecular delineation of the critical region. Am J Med Genet 55:33–37.PubMedCrossRefGoogle Scholar
  3. Barber MC, Clegg RA, Travers MT, Vernon RG (1997) Lipid metabolism in the lactating mammary gland. Biochim Biophys Acta 1347:101–126.PubMedCrossRefGoogle Scholar
  4. Casanueva FF, Dieguez C (1999) Neuroendocrine regulation and actions of leptin. Front Neuroendocrinol 20:317–363.PubMedCrossRefGoogle Scholar
  5. Chien EK, Hara M, Rovard M, Yano H, Phillipe M, Polonsky KS, Bell GI (1997) Increase in serum leptin and uterine leptin receptor messenger RNA levels during pregnancy in rats. Biochem Biophys Res Commun 237:476–480.PubMedCrossRefGoogle Scholar
  6. Cioffi JA, Shafer AW, Zupancic TJ, Smith-Gbur J, Mikhail A, Platika D, Snodgrass HR (1996). Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nature Med 2:585–589.PubMedCrossRefGoogle Scholar
  7. Dieguez C, Casanueva FF (2001) Ghrelin: a step forward in the understanding of somatotroph cell function and growth regulation. Eur J Endocrinol 142:413–417.CrossRefGoogle Scholar
  8. Edwards CM, Abusnana S, Sunter D, Murphy KG, Ghatei MA, Bloom SR (1999) The effects of orexins on food intake: comparisons with neuropeptide Y, melanin-concentarting hormone and galanin. J. Endocrinol 160:R7–R12.PubMedCrossRefGoogle Scholar
  9. Flier JS (1994) Leptin expression and action: new experimental paradigms. Proc Natl Acad Sci USA 94:4242–4245.CrossRefGoogle Scholar
  10. Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770.PubMedCrossRefGoogle Scholar
  11. Gavrilova O, Barr V, Marcus-Samuels B, Reitman M (1997) Hyperleptinemia of pregnancy associated with the appearance of a circulating form of the leptin receptor. J Biol Chem 272:30546–30551.PubMedCrossRefGoogle Scholar
  12. Gracia MC, Casanueva FF, Dieguez C, Señaris RM (2000) Gestational profile of leptin messenger ribonucleuc acid (mRNA) content in the placenta and adipose tissue in the rat, and regulation of the mRNA levels of the leptin receptor subtypes in the hypothalamus during pregnancy and lactation. Biol Reproduct 62:698–703.CrossRefGoogle Scholar
  13. Gualillo O, Caminos JE, Blanco M, Garcia-Caballero T, Kojima M, Kangawa K, Dieguez C, Casanueva FF (2001) Ghrelin, a novel placental-derived hormone. Endocrinology 142:788–794.PubMedCrossRefGoogle Scholar
  14. Horvath TL, Diano S, Sotonyi P, Heiman M, Tschop M (2001) Ghrelin and the regulation of energy balance a hypothalamic perspective. Endocrinology 142:4163–4169.PubMedCrossRefGoogle Scholar
  15. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS (1999) Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 20:68–100.PubMedCrossRefGoogle Scholar
  16. Kawai M, Yamaguchi M, Murakami T, Shima K, Murata Y, Kishi K (1997) The placenta is not the main source of leptin production in pregnant rat: gestational profile of leptin in plasma and adipose tissues. Biochem Biophys Res Commun 237:476–480.CrossRefGoogle Scholar
  17. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo M, Kangawa K (1999) Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature 402:656–660.PubMedCrossRefGoogle Scholar
  18. Lage M, Garcia-Mayor R, Tomé MA, Cordido F, Valle-Inclán F, Considine RV, Caro JF, Diéguez C, Casanueva FF (1999) Serum leptin levels in women throughout pregnancy and postpartum period and in women suffering spontaneous abortion. Clin Endocrinol 50:211–216.CrossRefGoogle Scholar
  19. Lee G, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. (1996) Abnormal splicing of the leptin receptor in diabetic mice. Nature 379:632–635.PubMedCrossRefGoogle Scholar
  20. Lopez M, Seoane LM, Garcia MC, Lago F, Casanueva FF, Señaris RM, Dieguez C. (2000) Leptin regulation of prepro-orexin and orexin receptor mRNA levies in the hypothalamus. Biochem Biophys Res Commun 269:41–45.PubMedCrossRefGoogle Scholar
  21. Masuzaki H, Ogawa Y, Sagawa N, Hosoda K, Matsumoto T, Mise H, Nishimura H, Yoshimasa Y, Tanaka I, Mori T, Nakao K (1997) Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nature Med 3:1029–1033.PubMedCrossRefGoogle Scholar
  22. Murakami T, Yamashita T, Iida M, Kuwajima M, Shima I (1997) A short form of leptin receptor performs signal transduction. Biochem Biophys Res Commun 231:26–29.PubMedCrossRefGoogle Scholar
  23. Okada K, Ishii S, Minami S, Sugihara H, Shibasaki T, Wakabayashi I (1996) Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats. Endocrinology 137:5155–5158.PubMedCrossRefGoogle Scholar
  24. Qu D, Ludwig DS, Gammeltoft S, Piper M, Pelleymounter MA, Cullen MJ, Mathes WF, Przypek R, Kanarek R, Maratos-Flier E (1996) A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Nature 380:243–247.PubMedCrossRefGoogle Scholar
  25. Richard D, Trayhurn P (1985) Energetic efficiency during pregnancy in mice fed ad libitum or pair-fed to the normal energy intake of unmated animals. J Nutr 115:593–600.PubMedGoogle Scholar
  26. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli R, Tanaka H, Williams S, Richardson R, Kozlowski G, Wilson S, Arch J, Buckingham R, haynes A, carr S, Annan R, MacNutty D, Li W, Terret J, Elshourbagy N, Bergsma D, Yanagisawa M (1998) Orexin and orexin receptors: a family of hypothalamic neuropeptides and G-protein-coupled receptors that regulate feeding behaviour. Cell 92:573–585.PubMedCrossRefGoogle Scholar
  27. Señaris R, García-Caballero T, Casabiell X, Gallego R, Castro R, Considine RV, Diéguez C, Casanueva FF (1997) Synthesis of leptin in human placenta. Endocrinology 138:4501–4504.PubMedCrossRefGoogle Scholar
  28. Tartaglia LA (1997) The leptin receptor. J Biol Chem 272:6093–6096.PubMedGoogle Scholar
  29. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Woolf EA, Monroe CA, Tepper RI (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83:1263–1271.PubMedCrossRefGoogle Scholar
  30. Tomimatsu T, Yamaguchi M, Murakami T, Ogura K, Sakata M, Mitsuda N, Kanzaki T, Kurachi H, Irahara M, Miyake A, Shima K, Aono T, Murata Y (1997) Increase of mouse leptin production by adipose tissue after midpregnancy: gestational profile of serum leptin concentration. Biochem Biophys Res Commun 240:213–215.PubMedCrossRefGoogle Scholar
  31. Torsello A, Luoni M, Schweiger F, Grilli R, Guidi M, Bresciani E, Deghenghi R, Muller EE, Locatelli V (1998) Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. Eur J Pharmacol 360:123–129.PubMedCrossRefGoogle Scholar
  32. Tschop M, Smiley DL, Helman ML (2000) Ghrelin induces adiposity in rodents. Nature 407:908–913.PubMedCrossRefGoogle Scholar
  33. White DW, Kuropatwinski KK, Devos R, Baumann H, Tartaglia LA (1997) Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homooligomerization. J Biol Chem 272:4065–4071.PubMedCrossRefGoogle Scholar
  34. Willesen MG, Kristensen P, Romer J (1999) Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology 70:306–316.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • M. C. García
    • 1
  • R. M. Señaris
    • 1
  • J. E. Caminos
    • 1
  • M. Lopez
    • 1
  • R. Nogueiras
    • 1
  • O. Gualillo
    • 1
  • F. Casanueva
    • 1
  • C. Diéguez
    • 1
  1. 1.Department of Physiology and Medicine, Faculty of MedicineUniversity of Santiago de CompostelaSpain

Personalised recommendations