Role of premature leptin surge in obesity resulting from intrauterine undernutrition.
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."
Yura
Shigeo
S
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan.
Itoh
Hiroaki
H
Sagawa
Norimasa
N
Yamamoto
Hiroshi
H
Masuzaki
Hiroaki
H
Nakao
Kazuwa
K
Kawamura
Makoto
M
Takemura
Maki
M
Kakui
Kazuyo
K
Ogawa
Yoshihiro
Y
Fujii
Shingo
S
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*
D020738:Leptin; D011257:Pregnancy Proteins