1998 Fiscal Year Final Research Report Summary
Molecular Medicine of Clinical Implication of Obese Gene Product
| Project/Area Number |
09671052
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
HOSODA Kiminori Kyoto University, Graduate School of Human and Environmental Studies, Assistant Professor, 大学院・人間・環境学研究科, 助手 (40271598)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Yoshihiro Kyoto University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究科, 助手 (70291424)
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| Project Period (FY) |
1997 – 1998
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| Keywords | leptin / uncoupling protein 3 / UCP / food inake / energy expenditure / white adipose tissue / insulin sensitivity / skeletal muscle |
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| Research Abstract |
(Purpose) We examined pathophysiological significance of leptin, and uncoupling protein 3 (UCP3) which appears to be downstream of leptin.
(Methods) We determined the structure of all exons of leptin receptor cDNA by direct sequencing in 17 Japanese obese subjects whose BMI is higher than 30 and who have family history of obesity. We determined allele frequency of polymorphisms of leptin receptor gene in 46 Japanese subjects with BMI > 30 and 64 subjects with BMI < 25 by SSCP and PCR-RFLP analyses. Using homology to mouse UCP2 cDNA, we cloned UCP3 cDNA from rat skeletal muscle. We examined UCP3 gene expression in rats fed high-fat diet. We investigated UCP3 gene expression in Wistar fatty rats treated with pioglitazone. We examined the UCP3 gene expression in primary mature adipocytes culture from rat epididymal fat.
(Results) We identified 7 polymorphisms in leptin receptor gene in Japanese morbidly obese subjects. No significant difference of allele frequency was noted between nonobese and morbidly obese subjects in all polymorphisms. UCP3 cDNA was cloned in rat skeletal muscle. Two-fold elevation of UCP3 gene expression was observed in rats fed high-fat diet. We observed significant increase of UCP3 gene expression by 2.1-fold in the epididymal fat, by 2.0-fold in the retroperitoneal fat, and by 1.6-fold in the brown fat. We observed significant increase of UCP3 gene expression by pioglitazone from the concentration of 10^<-5>M in rat primary white adipocyte culture.
(Discussion) Obesity in most of Japanese morbidy obese subjects can not be explained by leptin receptor gene polymorphisms. We cloned UCP3 cDNA from rat skeletal muscle. We demonstrated the increase of the UCP3 gene expression by high-fat diet feeding and by thiazolidines.
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