1998 Fiscal Year Final Research Report Summary
Control of metabolic diseases by means of brain function in mammals
| Project/Area Number |
08306016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKAHASHI Michio The University of Tokyo, Graduate School of Agricultural and Life Science, Professor, 大学院・農学生命科学研究科, 教授 (30011943)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Noboru Miyazaki University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (80150192)
TSUJIMOTO Hajime The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (60163804)
KAI Chieko The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (10167330)
MORI Yuji The University of Tokyo, Graduate School of Agricultural and Life Science, Profe, 大学院・農学生命科学研究科, 教授 (40157871)
NISHIHARA Masugi The University of Tokyo, Graduate School of Agricultural and Life Science, Assoc, 大学院・農学生命科学研究科, 助教授 (90145673)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Hypothalamus / Feeding behavior / Metabolism / Diabetes mellitus / Obesity / Growth hormone / Leptin / Transgenic rats |
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| Research Abstract |
The purpose of this study was to elucidate hypothalamic neuronal mechanisms controlling metabolism and feeding behavior and to regulate obesity, diabetes and abnormal feeding. We produced transgenic rats expressing human growth hormone (hGH), hGH receptor (hGHR) and leptin. The hGH transgenic rats showed excessive obesity due to the lack of endogenous GH pulses. On the other hand, in the bigenic rats expressing both hGH and hGHR, adipose tissue mass and serum leptin levels were decreased. These animals are useful models to analyze GH pulsatility and lipid metabolism. In the present study, we also examined the effect of injection of anti sense oligodeoxynucleotides (ODNs) of GABA synthetic enzyme, glutamic acid decarboxylase (GAD) that consists of two isozymes, GAD65 and GAD67, into the VMH of the male rat on food intake, body weight and locomotor activity. The results suggested that GAD65 was mainly involved in enhancing food intake and suppressing locomotor activity in rat VMH.This study also indicates that central injection of antisense oligodeoxynucleotides is useful means to regulate animal metabolism. From these studies, symptoms such as obesity, diabetes and abnormal feeding may be controlled by regulating GH pulsatility and gene expression of GAD 65 in they hypothalamus.
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