Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes
Capric Acid Up-Regulates UCP3 Expression without PDK4 Induction in Mouse C2C12 Myotubes
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DOI：
10.3177/jnsv.62.32
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发表时间：
2016-02-01
影响因子：
1.6
通讯作者：
Nikawa, Takeshi
中科院分区：
文献类型：
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作者：
Abe, Tomoki;Hirasaka, Katsuya;Nikawa, Takeshi
骨骼肌中的解偶联蛋白3 （UCP3）和丙酮酸脱氢酶激酶4 （PDK4）是参与胰岛素抵抗的葡萄糖和脂质代谢过程的关键调节因子。中链脂肪酸（MCFAs）对啮齿动物和人类具有抗肥胖作用，而长链脂肪酸（LCFAs）会导致体重增加和胰岛素抵抗。为了阐明MCFA的有益作用，我们检测了喂食MCFA或lcfa高脂肪饮食（HFD）的小鼠骨骼肌中UCP3和PDK4的表达。与喂食富含mcfa的HFD的小鼠相比，喂食富含lcfa的HFD五周后，小鼠体重增加，并诱导葡萄糖耐受不良。然而，喂食富含MCFA或lcfa的HFD的小鼠骨骼肌中UCP3和PDK4转录本的数量是相似的。为了进一步阐明MCFAs（如癸酸（C10:0））对骨骼肌脂质代谢的特定影响，我们在小鼠C2C12肌细胞中检测了各种FAs对UCP3和PDK4表达的影响。虽然棕榈酸（C16:0）和月桂酸（C12:0）显著诱导UCP3和PDK4的表达，但癸酸（C10:0）仅通过激活过氧化物酶体增殖物激活受体-6上调UCP3的表达。此外，棕榈酸（C16:0）干扰了胰岛素诱导的Akt磷酸化，而MCFAs，包括月桂酸（C12:0）、癸酸（C10:0）和辛酸（C12:0）则没有。这些结果表明，癸酸（C10:0）在不抑制骨骼肌糖酵解的情况下增加了脂肪酸氧化的能力。
Uncoupling protein 3 (UCP3) and pyruvate dehydrogenase kinase 4 (PDK4) in skeletal muscle are key regulators of the glucose and lipid metabolic processes that are involved in insulin resistance. Medium-chain fatty acids (MCFAs) have anti-obesogenic effects in rodents and humans, while long-chain fatty acids (LCFAs) cause increases in body weight and insulin resistance. To clarify the beneficial effects of MCFAs, we examined UCP3 and PDK4 expression in skeletal muscles of mice fed a MCFA- or LCFA-enriched high-fat diet (HFD). Five-week feeding of the LCFA-enriched HFD caused high body weight gain and induced glucose intolerance in mice, compared with those in mice fed the MCFA-enriched HFD. However, the amounts of UCP3 and PDK4 transcripts in the skeletal muscle of mice fed the MCFA- or LCFA-enriched HFD were similar. To further elucidate the specific effects of MCFAs, such as capric acid (C10:0), on lipid metabolism in skeletal muscles, we examined the effects of various FAs on expression of UCP3 and PDK4, in mouse C2C12 myocytes. Although palmitic acid (C16:0) and lauric acid (C12:0) significantly induced expression of both UCP3 and PDK4, capric acid (C10:0) upregulated only UCP3 expression via activation of peroxisome proliferator-activated receptor-6. Furthermore, palmitic acid (C16:0) disturbed the insulin-induced phosphorylation of Akt, while MCFAs, including lauric (C12:0), capric (C10:0), and caprylic acid (C12:0), did not. These results suggest that capric acid (C10:0) increases the capacity for fatty acid oxidation without inhibiting glycolysis in skeletal muscle.