Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: Effects on placental leptin and fetal growth

H Yamashita, J Shao, T Ishizuka, P J Klepcyk, P Muhlenkamp, L Qiao, Nigel Hoggard, J E Friedman

Research output: Contribution to journalArticle

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Abstract

Gestational diabetes mellitus (GDM) results from an interaction between susceptibility genes and the diabetogenic effects of pregnancy. During pregnancy, mice heterozygous for the lepin receptor (db/+) gain more weight, are glucose intolerant, and produce macrosomic fetuses compared with wild-type (+/+) mothers, suggesting that an alteration in leptin action may play a role in GDM and fetal overgrowth. To investigate whether leptin administration or pair-feeding can reduce adiposity and thereby prevent GDM and neonatal overgrowth, we examined energy balance, glucose and insulin tolerance, and fetal growth in pregnant db/+ and +/+ mice treated with recombinant human leptin-IgG during late pregnancy. Leptin reduced food intake and adiposity in pregnant db/+ mice to levels similar to pregnant +/+ mice and significantly reduced maternal weight gain. Maternal glucose levels were markedly lower during glucose and insulin challenge tests in leptin-treated db/+ mice relative to db/+ and pair-fed controls. Despite reduced energy intake and improved glucose tolerance, leptin administration did not reduce fetal overgrowth in offspring from db/+ mothers. Fetal and placental leptin levels were 1.3- to 1.5-fold higher in offspring from db/+ mothers and remained unchanged with leptin administration, whereas leptin treatment in +/+ mothers or pair-feeding decreased placental leptin concentration and reduced fetal birth weight. Our results provide evidence that leptin administration during late gestation can reduce adiposity and improve glucose tolerance in the db/+ mouse model of spontaneous GDM. However, fetal and placenta leptin levels are higher in db/+ mothers and are subject to reduced negative feedback in response to leptin treatment. These data suggest that alterations in placenta leptin may contribute to the regulation of fetal growth independently of maternal glucose levels.

Original languageEnglish
Pages (from-to)2888-2897
Number of pages10
JournalEndocrinology
Volume142
Issue number7
Publication statusPublished - Jul 2001

Keywords

  • normal glucose-tolerance
  • insulin-secretion
  • pancreatic-islets
  • obese women
  • longitudinal changes
  • skeletal-muscle
  • gene-expression
  • maternal serum
  • messenger-RNA
  • weight-gain

Cite this

Yamashita, H., Shao, J., Ishizuka, T., Klepcyk, P. J., Muhlenkamp, P., Qiao, L., ... Friedman, J. E. (2001). Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: Effects on placental leptin and fetal growth. Endocrinology, 142(7), 2888-2897.

Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: Effects on placental leptin and fetal growth. / Yamashita, H ; Shao, J ; Ishizuka, T ; Klepcyk, P J ; Muhlenkamp, P ; Qiao, L ; Hoggard, Nigel; Friedman, J E .

In: Endocrinology, Vol. 142, No. 7, 07.2001, p. 2888-2897.

Research output: Contribution to journalArticle

Yamashita, H, Shao, J, Ishizuka, T, Klepcyk, PJ, Muhlenkamp, P, Qiao, L, Hoggard, N & Friedman, JE 2001, 'Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: Effects on placental leptin and fetal growth', Endocrinology, vol. 142, no. 7, pp. 2888-2897.
Yamashita H, Shao J, Ishizuka T, Klepcyk PJ, Muhlenkamp P, Qiao L et al. Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: Effects on placental leptin and fetal growth. Endocrinology. 2001 Jul;142(7):2888-2897.
Yamashita, H ; Shao, J ; Ishizuka, T ; Klepcyk, P J ; Muhlenkamp, P ; Qiao, L ; Hoggard, Nigel ; Friedman, J E . / Leptin administration prevents spontaneous gestational diabetes in heterozygous Lepr(db/+) mice: Effects on placental leptin and fetal growth. In: Endocrinology. 2001 ; Vol. 142, No. 7. pp. 2888-2897.
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