| Co-Investigator(Kenkyū-buntansha) |
TOBE Takashi Showa University, School of Pharmaceutical Science, Full professor, 薬学部, 教授 (90102368)
TANIOKA Toshihiro Showa University, School of Pharmaceutical Science, Assistant professor, 薬学部, 助手 (80360585)
NEGORO Takaharu Showa University, School of Pharmaceutical Science, Assistant professor, 薬学部, 助手 (70218270)
KOBA Shinji Showa University, School of Medicine, Assistant professor, 医学部, 講師 (20276546)
YATSUDUKA Masashi Showa University, School of Medicine, Associate professor, 医学部, 助教授 (20119275)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Adiponectin is a protein exclusively secreted by adipocytes and exists in human plasma as at least three forms, i.e., a trimer, a hexamer and a high-molecular-weight (HMW) multimer.
1)The plasma adiponectin concentration, % of each adiponectin molecule, i.e., HMW, the hexamer and trimer, a gelatin-binding adiponectin ratio (gelatin-binding adiponectin/total adiponectin) and HMW/Total (HMW adiponectin concentration/Total adiponectin concentration) of each individual were analyzed.
Our novel ELISA using one of our monoclonal antibodies against HMW adiponectin is HMW adiponectin specific and with this ELISA, the HMW adiponectin concentrations were 7.8±4.9 μg/mL (mean±SD) in 159 clinically healthy women and 4.1±2.7 μg/mL (mean±SD) in 87 clinically healthy men, i.e., significantly lower (p<0.001). HMW concentration was negatively correlated with body weight, BMI, fat %, west size and TG, and positively with HDL-cholesterol.
Although, independent of the HMW adiponectin concentration, the ratio
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of HMW, and the hexamer and trimer in women's sera did not differ greatly, those in men's sera differed greatly. The men's sera with lower HMW concentrations exhibited lower HMW% and gelatin-binding adiponectin ratios.
2)The adiponectin concentrations in patients of coronary artery disease and diabetes mellitis (DM), and patients after surgical operations were analysed.
Both of HMW and total adiponectin concentrations were higher in patients than healthy subjects, which might be results of treatments.
By treatment of DM and hyperlipidemia, and weight reduction, and in cure process after surgical operation, HMW adiponectin concentration was increased faster than that of total adiponectin and these results suggested that HMW adiponectin might be a good monitoring parameter.
3)Using human adiponectn purified from human plasma, recombinant wild-type and mutant adiponectin, biological activities were analyzed.
HMW adiponectin inhibited differentiation of bone marrow macrophage to osteoclasts and induced secretion of anti-inflammatory cytokines. Moreover, these activities were positively correlated with affinity to gelatin. Less
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