Neonatal exposure to leptin augments diet-induced obesity in leptin-deficient ob/ob mice

Shigeo Yura, Hiroaki Itoh, Norimasa Sagawa, Hiroshi Yamamoto, Hiroaki Masuzaki, Kazuwa Nakao, Makoto Kawamura, Haruta Mogami, Yoshihiro Ogawa, Shingo Fujii

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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 and Procedures: 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. Discussion: 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.

Original languageEnglish
Pages (from-to)1289-1295
Number of pages7
JournalObesity
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 1 2008
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Yura, S., Itoh, H., Sagawa, N., Yamamoto, H., Masuzaki, H., Nakao, K., ... Fujii, S. (2008). Neonatal exposure to leptin augments diet-induced obesity in leptin-deficient ob/ob mice. Obesity, 16(6), 1289-1295. https://doi.org/10.1038/oby.2008.57