title: Role of premature leptin surge in obesity resulting from intrauterine undernutrition.
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."
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Itoh
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawamura
authors.forename: Maki
authors.initials: M
authors.lastname: Takemura
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Kakui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D020738:Leptin / Q000378:metabolism* / Q000502:physiology*; D044342:Malnutrition / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D009765:Obesity / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism / Q000502:physiology*; D014599:Uterus / Q000378:metabolism*
chemical_list: D020738:Leptin; D011257:Pregnancy Proteins