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Neonatal Overfeeding in Female Mice Predisposes the Development of Obesity in their Male Offspring via Altered Central Leptin Signalling.

Abstract
The prevalence of obesity among child-bearing women has increased significantly. The adverse consequences of maternal obesity on the descendants have been well accepted, although few studies have examined the underlying mechanisms. We investigated whether neonatal overfeeding in female mice alters metabolic phenotypes in the offspring and whether hypothalamic leptin signalling is involved. Neonatal overfeeding was induced by reducing the litter size to three pups per litter, in contrast to normal litter size of 10 pups per litter. Normal and neonatally overfed female mice were bred with normal male mice, and offspring of overfeeding mothers (OOM) and control mothers (OCM) were generated. We examined body weight, daily food intake, leptin responsiveness and the number of positive neurones for phosphorylated-signal transducer and activator of transcription 3 (pSTAT3) along with neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH) and NPY in the nucleus tractus solitarius (NTS) of the brain stem. The body weight and daily food intake of OOM were significantly higher than those of OCM. Leptin significantly reduced food intake and increased the number of pSTAT3 positive neurones in the ARH of OCM mice, whereas no significant changes in food intake and pSTAT3 neurones were found in leptin-treated OOM mice. The number of NPY neurones in the ARH and NTS of the OOM mice was significantly higher than that of OCM mice. The results of the present study indicate that the obese phenotype from mothers can be passed onto the subsequent generation, which is possibly associated with hypothalamic leptin resistance.
AuthorsH Wang, J Ji, Y Yu, X Wei, S Chai, D Liu, D Huang, Q Li, Z Dong, X Xiao
JournalJournal of neuroendocrinology (J Neuroendocrinol) Vol. 27 Issue 7 Pg. 600-8 (Jul 2015) ISSN: 1365-2826 [Electronic] United States
PMID25855235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 British Society for Neuroendocrinology.
Chemical References
  • Leptin
  • Neuropeptide Y
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
Topics
  • Animals
  • Animals, Newborn
  • Arcuate Nucleus of Hypothalamus (metabolism)
  • Eating (physiology)
  • Female
  • Leptin (metabolism)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neuropeptide Y (metabolism)
  • Obesity (metabolism)
  • STAT3 Transcription Factor (metabolism)
  • Signal Transduction (physiology)
  • Solitary Nucleus (metabolism)

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