| Project/Area Number |
15390504
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyoto University |
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Principal Investigator |
SAGAWA Norimasa Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (00162321)
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| Co-Investigator(Kenkyū-buntansha) |
KARIYA Masatoshi Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90243013)
ITOH Hiroaki Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (70263085)
YURA Shigeo Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (60335289)
OGAWA Yoshihiro Tokyo Medical and Dental University, School of Medicine, Professor, 医学研究科, 教授 (70291424)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 2004: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2003: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | pregnancy / placental formation / fetal growth retardation / leptin / life style disease / obesity / diet-induced thermogenesis / developmental origins of health and diseases / 胎盤 / インスリン抵抗性 / レジスチン / 胎児プログラミング |
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| Research Abstract |
Undernutrition in utero is closely associated with development of obesity in later life, relating to detrimental metabolic sequelae. We established a mouse model (C57/BL6) in which offspring with fetal undernutrition (UN offspring : 30% reduction of maternal food intake) on a high-fat diet develop pronounced adiposity (30% increase in fat deposit). In the neonatal catch-up period, UN offspring exhibited leptin surge at earlier time (premature leptin surge) compared to offspring with intrauterine normal nutrition (NN offspring). Using this animal model, we demonstrated the possible involvement of premature leptin surge in the developmental origins of obesity. On a high fat diet, NN offspring neonatally treated with leptin (NN-Lep offspring) developed pronounced obesity (30% increase in fat deposit) compared to vehicle-treated groups. Both UN offspring and NN-Lep offspring exhibited an impaired response to peripheral (i.p.), but not to central (i.c.v.), leptin administration in all param
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eters, decrease in calorie intake, body weight loss, hypothalamic phosphorylation of STAT3, and the number of c-Fos positive cells in ARH. These observations indicated the impaired leptin transport to the brain, so called leptin resistance state, which may be causatively involved in augmentation in high fat diet-induced obesity. Thus, NN-Lep offspring showed a phenotype indistinguishable from that of UN offspring. On the other hand, in leptin deficient ob/ob mice offspring, undernutrition in utero did not cause augmentation of high fat diet-induced obesity nor resistance to peripheral leptin treatment. Moreover, the ob/ob offspring with neonatal leptin treatment exhibited body weight changes when they were fed with regular chow diet as those treated with saline vehicle during neonatal period. However, on a high fat diet, they developed more severe obesity as compared to that in vehicle treated group. Premature leptin surge plays crucial roles in the developmental origins of obesity in offspring exposed to intrauterine undernutrition. Less
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