title: Creatine inhibits adipogenesis by downregulating insulin-induced activation of the phosphatidylinositol 3-kinase signaling pathway.
abstract: Creatine is a nitrogenous organic acid known to function in adenosine triphosphate (ATP) metabolism. Recent evidence indicates that creatine regulates the differentiation of mesenchymal stem cells (MSCs) in processes such as osteogenesis and myogenesis. In this study, we show that creatine also has a negative regulatory effect on fat cell formation. Creatine inhibits the accumulation of cytoplasmic triglycerides in a dose-dependent manner irrespective of the adipogenic cell models used, including a C3H10T1/2 MSC line, 3T3-L1 preadipocytes, and primary human MSCs. Consistently, a dramatic reduction in mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), glucose transporters, 1 and 4 (Glut1, Glut4), and adipocyte markers, aP2 and adipsin, was observed in the presence of creatine. Creatine appears to exert its inhibitory effects on adipogenesis during early differentiation, but not late differentiation, or proliferation stages through inhibition of the PI3K-Akt-PPARγ signaling pathway. In an in vivo model, administration of creatine into mice resulted in body mass increase without fat accumulation. In summary, our results indicate that creatine downregulates adipogenesis through inhibition of phosphatidylinositol 3-kinase (PI3K) activation and imply the potent therapeutic value of creatine in treating obesity and obesity-related metabolic disorders.
authors.affiliation: 1 College of Biotechnology and Bioengineering, Sungkyunkwan University , Suwon, Gyeonggi-Do, Republic of Korea.
authors.forename: Nayeon
authors.initials: N
authors.lastname: Lee
authors.forename: Inhee
authors.initials: I
authors.lastname: Kim
authors.forename: Soojeong
authors.initials: S
authors.lastname: Park
authors.forename: Dasol
authors.initials: D
authors.lastname: Han
authors.forename: Soobong
authors.initials: S
authors.lastname: Ha
authors.forename: Mookwang
authors.initials: M
authors.lastname: Kwon
authors.forename: Juwan
authors.initials: J
authors.lastname: Kim
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Byun
authors.forename: Wonil
authors.initials: W
authors.lastname: Oh
authors.forename: Hong Bae
authors.initials: HB
authors.lastname: Jeon
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Kweon
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
mesh_terms: D016475:3T3 Cells; D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D011416:Complement Factor D / Q000235:genetics / Q000378:metabolism; D003401:Creatine / Q000494:pharmacology*; D015536:Down-Regulation; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D050556:Fatty Acid-Binding Proteins; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D047495:PPAR gamma; D014280:Triglycerides; D019869:Phosphatidylinositol 3-Kinases; D011416:Complement Factor D; D003401:Creatine