title: Honokiol enhances adipocyte differentiation by potentiating insulin signaling in 3T3-L1 preadipocytes.
abstract: Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with rosiglitazone. During adipocyte differentiation, the expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) mRNA and PPARγ target genes such as adipocyte protein 2 (aP2), adiponectin, and GLUT4 was induced by treatment with 10 μM honokiol. However, honokiol failed to show direct binding to the PPARγ ligand-binding domain in vitro. In preadipocytes, treatment with honokiol in the presence of insulin increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 protein and Akt protein, early insulin signaling pathways related to adipocyte differentiation, compared with insulin-only treatment. Taken together, our results suggest that honokiol promotes adipocyte differentiation through increased expression of PPARγ2 mRNA and potentiation of insulin signaling pathways such as the Ras/ERK1/2 and phosphoinositide-3-kinase (PI3K)/Akt signaling pathways.
authors.affiliation: Research Institute for Biological Functions, Chubu University, 1200 Matsumoto, Kasugai, Aichi, 487-8501, Japan.
authors.forename: Sun-Sil
authors.initials: SS
authors.lastname: Choi
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
authors.forename: Kagami
authors.initials: K
authors.lastname: Iida
authors.forename: Masako
authors.initials: M
authors.lastname: Sato
authors.forename: Young-Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Teruya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagai
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D031566:Magnolia / Q000737:chemistry; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D007328:Insulin; D017705:Lignans; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051057:Proto-Oncogene Proteins c-akt; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols