title: Bisphenol a accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway.
abstract: In order to identify whether bisphenol A (BPA) acts as an adipogenic agent, following the hormonal induction of differentiation into adipocytes, 3T3-L1 cells were treated for six days with BPA alone. Treatment with BPA increased the triacylglycerol (TG) content of the cultures, increased the percentage of Oil Red O-staining cells in the cultures, and increased the levels of lipoprotein lipase (LPL) and adipocyte-specific fatty acid binding protein (aP2) mRNAs. These findings indicate that BPA was able to accelerate terminal differentiation of 3T3-L1 cells into adipocytes. LY294002, a chemical inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), blocked completely the increasing effect of BPA on TG accumulation and expression of LPL and aP2 mRNAs. Western blot analysis revealed that BPA increased the level of phosphorylated Akt kinase. Based on these findings, we concluded that BPA acted through the PI 3-kinase and Akt kinase pathway, resulting in increased TG accumulation and expression of adipocyte genes. The structure-activity relationship for BPA-related chemicals was examined. Eight derivatives of BPA (three diphenylalkanes with different substituents at the central carbon atom, three diphenylalkanes with ester bonds on hydroxyl groups in the phenolic rings, one bisphenol consisting of a sulphur atom at the central position, one chemical with cyanic groups, instead of hydroxyl groups, in the phenolic rings) accelerated terminal adipocyte differentiation and their potencies to increase TG accumulation were 73-97% of that of BPA. Two diphenylalkanes with ether bonds on hydroxyl groups and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) did not have the ability to accelerate terminal adipocyte differentiation.
authors.affiliation: Department of Medical Technology, Faculty of Health Sciences, Ehime Prefectural University of Health Sciences, Iyo-gun, Ehime 791-2101, Japan. hmasuno@epu.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masuno
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Teruki
authors.initials: T
authors.lastname: Kidani
authors.forename: Kenshi
authors.initials: K
authors.lastname: Sakayama
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Honda
mesh_terms: D041721:3T3-L1 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D001391:Azo Compounds; D001559:Benzhydryl Compounds; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D050556:Fatty Acid-Binding Proteins; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013194:Staining and Labeling; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001391:Azo Compounds; D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D050556:Fatty Acid-Binding Proteins; D008071:Lipoprotein Lipase; D009025:Morpholines; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014280:Triglycerides; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C011049:oil red O; C006780:bisphenol A; D000098826:Bisphenol A Compounds