Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan.
Genes Cells. 2011 Jun;16(6):681-91. doi: 10.1111/j.1365-2443.2011.01517.x. Epub 2011 Apr 18.
We studied the relationship between fatty acid-binding protein 3 (FABP3) and obesity in vivo and the effects of FABP3 on signal transduction for glucose uptake in skeletal muscle cells in vitro. In obese mice, the level of FABP3 protein in gastrocnemius muscles increased significantly with an increase in body weight and metabolic phenotypes, suggesting a close relationship between FABP3 expression in the muscle and the development of obesity and/or insulin resistance in mice. In experiments using C2C12 myotubes infected with adenoviruses encoding human FABP3, induction stimulated glucose uptake without insulin stimulation in parallel with increases in the phosphorylation of AMP-activated protein kinase (AMPK) and AS160. Insulin enhanced glucose uptake in an additive fashion with increased phosphorylation of Akt and AS160 in FABP3-induced myotubes compared to control cells. This increased glucose uptake in FABP3-induced myotubes with insulin stimulation was found even in the presence of palmitate, in which a significantly higher Akt phosphorylation was detected compared to controls. These results suggest that FABP3 stimulates glucose uptake by facilitating AMPK-dependent AS160 phosphorylation in skeletal muscle. FABP3 may also contribute to AS160 phosphorylation by maintaining insulin-dependent Akt activation in the cells under a lipotoxic condition.
我们研究了脂肪酸结合蛋白 3（FABP3）在体内与肥胖的关系，以及 FABP3 对体外骨骼肌细胞葡萄糖摄取信号转导的影响。在肥胖小鼠中，腓肠肌中 FABP3 蛋白水平随着体重和代谢表型的增加而显著升高，提示肌肉中 FABP3 的表达与肥胖和/或胰岛素抵抗的发生密切相关。在使用腺病毒感染编码人 FABP3 的 C2C12 肌管的实验中，诱导平行于 AMP 激活蛋白激酶（AMPK）和 AS160 的磷酸化增加而刺激无胰岛素刺激的葡萄糖摄取。与对照细胞相比，与 Akt 和 AS160 的磷酸化增加相比，胰岛素以相加的方式增强 FABP3 诱导的肌管中的葡萄糖摄取。在存在棕榈酸的情况下，即使在存在棕榈酸的情况下，也发现 FABP3 诱导的肌管中的葡萄糖摄取增加，与对照相比，检测到明显更高的 Akt 磷酸化。这些结果表明，FABP3 通过促进骨骼肌中 AMPK 依赖性 AS160 磷酸化来刺激葡萄糖摄取。FABP3 还可以通过在脂肪毒性条件下维持细胞中胰岛素依赖性 Akt 激活来促进 AS160 磷酸化。
