RRC ID 56130
Author Takeno A, Kanazawa I, Notsu M, Tanaka KI, Sugimoto T.
Title Phloretin Promotes Adipogenesis via Mitogen-Activated Protein Kinase Pathways in Mouse Marrow Stromal ST2 Cells.
Journal Int J Mol Sci
Abstract Phloretin, a glucose transporter (GLUT) inhibitor, has pleiotropic effects. The present study examined the effects of phloretin on the commitment of marrow stromal cells to adipocytes, using the mouse marrow stromal cell line ST2. Oil red O staining showed that treatment with phloretin 10⁻100 µM promoted lipid accumulation. Real-time PCR showed that phloretin significantly increased the expression of adipogenic markers, including PPARγ, C/EBPα, fatty acid synthase, fatty acid-binding protein 4, and adiponectin. Western blotting showed that phloretin inhibited ERK1/2 and JNK but activated p38 MAPK. Treatment with a MAPK/ERK kinase inhibitor and a JNK inhibitor enhanced adipogenesis, similar to phloretin. In contrast, a p38 MAPK inhibitor suppressed phloretin-induced adipogenesis. Although phloretin phosphorylated AMP-activated protein kinase (AMPK), co-incubation with an AMPK inhibitor did not block phloretin-induced adipogenesis. The 2-deoxyglucose colorimetric assay showed that phloretin and siRNA silencing of GLUT1 decreased glucose uptake. However, unlike phloretin treatment, GLUT1 silencing inhibited adipogenesis. In addition, phloretin enhanced adipogenesis in GLUT1 knocked-down cells. Taken together, phloretin induced adipogenesis of marrow stromal cells by inhibiting ERK1/2 and JNK and by activating p38 MAPK. The adipogenic effects of phloretin were independent of glucose uptake inhibition. Phloretin may affect energy metabolism by influencing adipogenesis and adiponectin expression.
Volume 19(6)
Published 2018-6-14
DOI 10.3390/ijms19061772
PII ijms19061772
PMID 29904032
PMC PMC6032296
MeSH Adipogenesis* Adiponectin / genetics Adiponectin / metabolism Animals Bone Marrow Cells / cytology Bone Marrow Cells / drug effects* Bone Marrow Cells / metabolism Cell Line Fatty Acid Synthases / genetics Fatty Acid Synthases / metabolism Fatty Acid-Binding Proteins / genetics Fatty Acid-Binding Proteins / metabolism Glucose Transporter Type 1 / genetics Glucose Transporter Type 1 / metabolism MAP Kinase Signaling System* Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / drug effects* Mesenchymal Stem Cells / metabolism Mice Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism PPAR gamma / genetics PPAR gamma / metabolism Phloretin / pharmacology* Protein Kinases / metabolism p38 Mitogen-Activated Protein Kinases / metabolism
IF 4.183
Times Cited 3
Human and Animal Cells ST2(RCB0224)