2006 Fiscal Year Final Research Report Summary
An experimental and clinical study on the development of adult disease in offspring with intrauterine undernutrition
| Project/Area Number |
17390450
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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 | Mie University |
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Principal Investigator |
SAGAWA Norimasa Mie University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (00162321)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Takashi Mie University, University Hospital, Associate Professor, 医学部附属病院, 助教授 (10263005)
TABATA Tsutomu Mie University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (40252358)
ITOH Hiroaki National Hospital Organization, Osaka National Hospital, Medical Doctor, 産婦人科, 医員 (70263085)
YURA Shigeo Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (60335289)
MASUZAKI Hiroaki Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00291899)
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| Project Period (FY) |
2005 – 2006
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| Keywords | pregnancy / intrauterine nutrition / fetal growth restriction / leptin / adult disease / obesity / hypertension / rennin angiotensin system |
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| Research Abstract |
Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We established 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. In leptin deficient ob/ob mice, intrauterine undernutrition did not caused pronounced obesity on anHFD. However, artificial premature le
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ptin surge in early neonatal period of this ob./ob mice resulted in a significant obesity on an HFD.
Wild type UN offspring showed an increase in systolic blood pressure (8 weeks of age; wks, P<0.05 and 16 wks, P<0.01), perivascular fibrosis of the coronary artery (16 wks, P<0.05) and cardiomegaly (16 wks, P<0.01) and cardiomyocyte nlargement, concomitant with a significant augmentation of angiotensinogen (Ang, P<0.05) and endothelin-1 (ET-1, P<0.01) mRNA expression and a tendency of increase in both angiotensin II and ET-1 immunostaining in the left ventricles (16 wks)
These findings suggest that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and diseases" and that fetal undernutrition activated the local cardiac angiotensin system associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure. Less
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