title: 13-Methylberberine, a berberine analogue with stronger anti-adipogenic effects on mouse 3T3-L1 cells.
abstract: Lipid metabolism modulation is a main focus of metabolic syndrome research, an area in which many natural and synthetic chemicals are constantly being screened for in vitro and in vivo activity. Berberine, a benzylisoquinoline plant alkaloid, has been extensively investigated for its anti-obesity effects and as a potential cholesterol and triglyceride-lowering drug. We screened 11 protoberberine and 2 benzophenanthridine alkaloids for their anti-adipogenic effects on 3T3-L1 adipocytes and found that 13-methylberberine exhibited the most potent activity. 13-Methylberberine down-regulated the expression of the main adipocyte differentiation transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT enhancer binding protein alpha (C/EBPα), as well as their target genes. PPARγ, C/EBPα, and sterol regulatory element binding protein 1 (SREBP-1) protein levels were reduced, and this lipid-reducing effect was attenuated by an AMP-activated protein kinase (AMPK) inhibitor, indicating that the effect of this compound requires the AMPK signaling pathway. Decreased Akt phosphorylation suggested reduced de novo lipid synthesis. C-13 methyl substitution of berberine increased its accumulation in treated cells, suggesting that 13-methylberberine has improved absorption and higher accumulation compared to berberine. Our findings suggest that 13-methylberberine has potential as an anti-obesity drug.
authors.affiliation: Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kitashirakawa, Sakyo, Kyoto, 606-8502, Japan.
authors.forename: Yit-Lai
authors.initials: YL
authors.lastname: Chow
authors.affiliation: Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kitashirakawa, Sakyo, Kyoto, 606-8502, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Sogame
authors.affiliation: Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kitashirakawa, Sakyo, Kyoto, 606-8502, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000470:Alkaloids; D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D010936:Plant Extracts; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D001599:Berberine; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases