title: Coenzyme Q10 increases the fatty acid oxidation through AMPK-mediated PPARα induction in 3T3-L1 preadipocytes.
abstract: Coenzyme Q10(CoQ10) is a known anti-adipogenic factor. However, the mechanism by which CoQ10 acts is unclear. In this study, we found that CoQ10 increased the phosphorylation of AMP-activated protein kinase (AMPK) in 3T3-L1preadipocytes. CoQ10 induced an increase in cytoplasmic calcium concentrations, which is reflected by increased Fluo-3 intensity under confocal microscopy recording. Either inhibition of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) or knock-down CaMKK blocked CoQ10-induced AMPK phosphorylation, suggesting the involvement of calcium in CoQ10-mediated AMPK signaling. CoQ10 also increased the expression of peroxisome proliferator-activated receptor alpha (PPARα) at both the mRNA and protein levels. Knock down of AMPK with siRNA or inhibition of AMPK using an AMPK inhibitor compound C blocked CoQ10-induced expression of PPARα, indicating that AMPK plays a critical role in PPARα induction. In addition, CoQ10 increased fatty acid oxidation in 3T3-L1preadipocytes. The promoter activity of PPARα was increased by CoQ10 in an AMPK-dependent fashion. Moreover, the induction of acyl-CoA oxidase (ACO), a target gene of PPARα, was blocked under the PPARα knock down condition. Furthermore, treatment with CoQ10 blocked differentiation-induced adipogenesis. This blockade was not observed under the PPARα knock-down condition. Collectively, these results demonstrate that CoQ10 induces PPARα expression via the calcium-mediated AMPK signal pathway and suppresses differentiation-induced adipogenesis.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Kim
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.forename: Ga Young
authors.initials: GY
authors.lastname: You
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.forename: Jie
authors.initials: J
authors.lastname: Sha
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042962:Acyl-CoA Oxidase / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D047493:PPAR alpha; D034741:RNA, Small Interfering; D014451:Ubiquinone; D042962:Acyl-CoA Oxidase; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; C024989:coenzyme Q10; D002118:Calcium