title: Neonatal exposure to leptin augments diet-induced obesity in leptin-deficient Ob/Ob mice.
abstract: OBJECTIVE
  Epidemiological evidence has revealed that undernutrition in utero is closely associated with obesity and related detrimental metabolic sequelae in adulthood. Recently, using a wild-type (wt) mouse model in which offspring were exposed to intrauterine undernutrition (UN offspring), we reported that the premature leptin surge during neonatal growth promotes lifelong changes in energy regulating circuitry in the hypothalamus, thus playing an important role in the development of pronounced obesity on a high-fat diet (HFD) in adulthood. Here, we further evaluate the essential involvement of leptin in the developmental origins of obesity using leptin-deficient ob/ob mice.
  
  
  METHODS
  We assessed the progression of obesity on an HFD in adult leptin-deficient ob/ob male mice that were exposed to intrauterine undernutrition by maternal food restriction (ob/ob UN offspring) or to leptin treatment during the neonatal period; this treatment is comparable to the premature leptin surge observed in the wt-UN offspring.
  
  
  RESULTS
  On an HFD, the body weight of the male ob/ob UN offspring paralleled that of the ob/ob offspring exposed to normal intrauterine nutrition (ob/ob NN offspring). In contrast, early exposure to leptin in the ob/ob NN offspring during early neonatal growth reproduced the development of pronounced obesity on an HFD in adulthood.
  
  
  CONCLUSIONS
  The presence of leptin and associated energy regulation are indispensable in the acceleration of obesity on an HFD caused by undernutrition in utero. The premature leptin surge plays an essential role in the developmental origins of obesity as a programming signal during the early neonatal period.
authors: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. psuka@kuhp.kyoto-u.ac.jp
authors: Shigeo
authors: S
authors: Yura
authors: Hiroaki
authors: H
authors: Itoh
authors: Norimasa
authors: N
authors: Sagawa
authors: Hiroshi
authors: H
authors: Yamamoto
authors: Hiroaki
authors: H
authors: Masuzaki
authors: Kazuwa
authors: K
authors: Nakao
authors: Makoto
authors: M
authors: Kawamura
authors: Haruta
authors: H
authors: Mogami
authors: Yoshihiro
authors: Y
authors: Ogawa
authors: Shingo
authors: S
authors: Fujii
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008297:Male; D044342:Malnutrition / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology* / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D015430:Weight Gain / Q000502:physiology
chemical_list: D004041:Dietary Fats; D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin