| Project/Area Number |
12670735
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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 |
Pediatrics
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
ASAYAMA Kohtaro University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (70129310)
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| Co-Investigator(Kenkyū-buntansha) |
DOBASHI Kazushige University of Occupational and Environmental Health, School of Medicine, Research Associate, 医学部, 助手 (60260569)
MIYAGAWA Takayuki University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 講師 (90219733)
KAWADA Yasusada University of Occupational and Environmental Health, School of Medicine, Research Associate, 医学部, 助手 (10204736)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Life-style related diseases / Adipose tissue / Antioxidant enzymes / Frdd radicals / Nitric oxide / Obesity / Child |
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| Research Abstract |
1. Inducible nitric oxide syntase (iNOS) was induced when differentiated 3T3-L1 preadipocyte were incubated in the presence of lipopolysaccharide (LPS), tumor necrosis factor-a (TNF-α) and interferon-γ. Nitric oxide (NO) production was enhanced. Such process was blocked by the co-incubation with troglitazone.
2. Incubation of cultured brown adipocytes with LPS and TNF-α resulted in the induction of iNOS accompanied by an enhanced production of NO.
3. OLETF obese diabetic rats and their lean counterparts (LETO rats) were fed diet with and without addition of troglitazone. Intraperitoneal injection of LPS resulted in a greater induction of adipose tissue iNOS associated with NO production in the OLETF rats than in the LETO rats. Troglitazone inhibited such reaction.
4. Both cellular and extracellular glutathione peroxidase (GPX) were increased in the kidneys of obese rats, while those were decreased in the adipose tissue.
5. Protein carbonyl groups (PCG) and TNF- were increased in the serum of obese rats, while troglitazone suppressed the increase.
6. Both PCG and the antibodies against oxidized LDL were increased in the serum of obese children, suggesting that oxidative stress was enhanced in these children.
7. Protein kinase A system exerted a differential effect on iNOS induction in brown and white adipose tissues. Forskolin and c-AMP were inhibitory to the white adipocytes, but stimulatory to the brown adipocytes.
8. Cellular GPX was inactivated by NO in cultured KNRK cells, leading to the subsequent induction of the mRNA as the protective mechanism. Extracellular GPX was also inactivated in vitro, whereas in vivo induction of iNOS by the administration of LPS to the rat resulted in the increase in extracellular GPX in serum.
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