title: Cilostazol induces mitochondrial fatty acid β-oxidation in C2C12 myotubes.
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.
authors.affiliation: Department of Internal Medicine, South Branch of Yantaishan Hospital, Yantai 264025, Shandong Province, China. Electronic address: wangbo6861@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Zhucheng City People's Hospital, Zhucheng 262200, Shandong Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, YanTai Development Zone Hospital, Yantai 264004, Shandong Province, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Sui
authors.affiliation: Department of Endocrinology, Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine, South Branch of Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Internal Medicine, South Branch of Yantaishan Hospital, Yantai 264025, Shandong Province, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Ren
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002460:Cell Line; D000077407:Cilostazol; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D035941:Iron Regulatory Protein 1 / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D018955:CD36 Antigens; D015820:Cadherins; D002334:Carnitine O-Palmitoyltransferase; D000077407:Cilostazol; D017362:Cyclic AMP Response Element-Binding Protein; D005227:Fatty Acids; D035941:Iron Regulatory Protein 1; D007546:Isoquinolines; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D013449:Sulfonamides; D013777:Tetrazoles; D014157:Transcription Factors; D014280:Triglycerides; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse; C070896:M-cadherin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Cilostazol; Fatty acid β-oxidation; Metabolic diseases; PGC-1α