Cilostazol induces mitochondrial fatty acid β-oxidation in C2C12 myotubes |
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Authors: | Bo Wang Liping Zhu Shaohua Sui Caixia Sun Haiping Jiang Donghui Ren |
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Institution: | 1. Department of Internal Medicine, South Branch of Yantaishan Hospital, Yantai 264025, Shandong Province, China;2. Department of Endocrinology, Zhucheng City People’s Hospital, Zhucheng 262200, Shandong Province, China;3. Department of Endocrinology, YanTai Development Zone Hospital, Yantai 264004, Shandong Province, China;4. Department of Endocrinology, Yantaishan Hospital, Yantai 264025, Shandong Province, China |
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Abstract: | Cilostazol is a drug licensed for the treatment of intermittent claudication. Its main action is to elevate intracellular levels of cyclic monophosphate (cAMP) by inhibiting the activity of type III phosphodiesterase, a cAMP-degrading enzyme. The effects of cilostazol on fatty acid oxidation (FAO) are as yet unknown. In this study, we report that cilostazol can elevate complete FAO and decrease both triacylglycerol (TAG) accumulation and TAG secretion. This use of cilostazol treatment increases expression of PGC-1α and, subsequently, its target genes, such as ERRα, NOR1, CD36, CPT1, MCAD, and ACO. Expression of these factors is linked to fatty acid β-oxidation but this effect is inhibited by H-89, a specific inhibitor of the PKA/CREB pathway. Importantly, knockdown of PGC-1α using siRNA abolished the effects of cilostazol in fatty acid oxidation (FAO) and TAG metabolism. These findings suggested that the PKA/CREB/PGC-1α pathway plays a critical role in cilostazol-induced fatty acid oxidation and TAG metabolism. |
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Keywords: | Cilostazol PGC-1α Metabolic diseases Fatty acid β-oxidation |
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