| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Research Abstract |
Experiment # 1. The catalytically inactive form of lipoprotein lipase (LPL) is detectable at high levels in serum, although its physiological role remained unknown. The aim of this study was to elucidate its clinical significance. We measured the LPL mass before and 15 min after the injection of heparin in 164 subjects with hyperlipidemia. LPL mass was measured by a sensitive sandwich enzyme-linked immunosorbent assay. Serum LPL was one-fifth of the postheparin LPL concentration. There was a weak correlation between the serum LPL and postheparin LPL. The delta LPL (post minus pre) was strongly related to the postheparin LPL, but not to the preheparin LPL mass, suggesting that the weak correlation between serum LPL and postheparin LPL levels was attributable to contamination of postheparin plasma by pre-existing LPL. Both serum and postheparin LPL were significantly lower in diabetic patients, and in subjects with high levels of TG or low levels of HDL. Serum LPL was correlated negative
… More
ly with remnants, and insulin resistance, and was correlated positively with HDL cholesterol and LDL size. Postheparin LPL was strongly correlated with HDL cholesterol, but not with other parameters as was serum LPL. Delta LPL mass did not show closer association with TG metabolism than postheparin LPL or preheparin LPL. In conclusion, serum LPL measurement is simple and seems to be useful for studying TG metabolism.
Experiment # 2. We examined the effects of pioglitazone, an insulin sensitizer, on mRNA levels of LPL in both tissues of brown adipose tissue-deficient (BAT-less) mice which develops insulin resistance and hyper-TG. Both LPL mRNA of WAT and SM were halved in BAT-less compared with wild-type mice. Pioglitazone increased LPL mRNA in the epididymal WAT by 8-fold, which was substantially associated with 4-fold increased PPAR-γ mRNA in the WAT. In contrast, pioglitazone did not affect LPL mRNA in the lower-limb SM. These results suggest that pioglitazone exclusively increases LPL production in WAT via stimulating PPAR-γ. No change of LPL production in SM by pioglitazone would be beneficial for preventing the development of insulin resistance due to increased delivery of fatty acids to muscle. Less
|
