Department of Integrative Physiology & Bio-System Control, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Biochem Biophys Res Commun. 2013 Apr 12;433(3):281-5. doi: 10.1016/j.bbrc.2013.02.101. Epub 2013 Mar 18.
Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA-PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance.
关于脂质对骨骼肌细胞影响的研究很少涉及溶血磷脂的影响。通过我们最近的研究，我们发现了一些特定形式的磷脂，如烷基-LPA，是细胞内受体过氧化物酶体增殖物激活受体γ（PPARγ）的配体。PPARγ 是一种核激素受体，与许多人类疾病有关，包括糖尿病和肥胖症。我们之前表明，烷基-LPA 是 PPARγ 的一种特异性激动剂。然而，烷基-LPA-PPARγ 轴如何影响骨骼肌细胞的机制尚不清楚。本研究的目的是确定烷基-LPA 和 PPARγ 激活是否促进骨骼肌细胞摄取葡萄糖。我们的研究结果表明，C2C12 细胞中 PPARγ1 mRNA 的丰度高于 PPARγ2 mRNA。我们表明，烷基-LPA（3 μM）可显著激活 PPARγ 并增加骨骼肌细胞内的葡萄糖水平。我们还表明，用烷基-LPA 孵育 C2C12 细胞会导致细胞内脂质积累。这些发现表明，在没有胰岛素的情况下，烷基-LPA 可激活 PPARγ 并刺激 C2C12 细胞摄取葡萄糖。这可能有助于治疗胰岛素抵抗时降低血浆葡萄糖水平。
