Kageyama Haruaki, Hirano Tsutomu, Okada Kenta, Ebara Tetsu, Kageyama Asako, Murakami Toru, Shioda Seiji, Adachi Mitsuru
First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Biochem Biophys Res Commun. 2003 May 23;305(1):22-7. doi: 10.1016/s0006-291x(03)00663-6.
Lipoprotein lipase (LPL), a key enzyme for triglyceride hydrolysis, is an insulin-dependent enzyme and mainly synthesized in white adipose tissue (WAT) and skeletal muscles (SM). To explore how pioglitazone, an enhancer of insulin action, affects LPL synthesis, we examined the effect of pioglitazone on LPL mRNA levels in WAT or SM of brown adipose tissue (BAT)-deficient mice, which develop insulin resistance and hypertriglyceridemia. Both LPL mRNA of WAT and SM were halved in BAT-deficient mice. Pioglitazone increased LPL mRNA in WAT by 8-fold, which was substantially associated with a 4-fold increase of peroxisome proliferator activated receptor (PPAR)-gamma mRNA (r=0.97, p<0.0001), whereas pioglitazone did not affect LPL mRNA in SM. These results suggest that pioglitazone exclusively increases LPL production in WAT via stimulation of PPAR-gamma synthesis. Since pioglitazone does not affect LPL production in SM, this would contribute to prevent the development of insulin resistance due to lipotoxicity.
脂蛋白脂肪酶（LPL）是甘油三酯水解的关键酶，是一种胰岛素依赖酶，主要在白色脂肪组织（WAT）和骨骼肌（SM）中合成。为了探究胰岛素作用增强剂吡格列酮如何影响LPL合成，我们检测了吡格列酮对棕色脂肪组织（BAT）缺陷小鼠的WAT或SM中LPL mRNA水平的影响，这些小鼠会出现胰岛素抵抗和高甘油三酯血症。BAT缺陷小鼠的WAT和SM中的LPL mRNA均减半。吡格列酮使WAT中的LPL mRNA增加了8倍，这与过氧化物酶体增殖物激活受体（PPAR）-γ mRNA增加4倍显著相关（r = 0.97，p <0.0001），而吡格列酮对SM中的LPL mRNA没有影响。这些结果表明，吡格列酮通过刺激PPAR-γ合成专门增加WAT中的LPL产生。由于吡格列酮不影响SM中的LPL产生，这将有助于预防因脂毒性导致的胰岛素抵抗的发展。
