Role of premature leptin surge in obesity resulting from intrauterine undernutrition

Shigeo Yura, Hiroaki Itoh, Norimasa Sagawa, Hiroshi Yamamoto, Hiroaki Masuzaki, Kazuwa Nakao, Makoto Kawamura, Maki Takemura, Kazuyo Kakui, Yoshihiro Ogawa, Shingo Fujii

Research output: Contribution to journalArticlepeer-review

324 Citations (Scopus)

Abstract

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease.".

Original languageEnglish
Pages (from-to)371-378
Number of pages8
JournalCell metabolism
Volume1
Issue number6
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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