Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway.
Berberine (BBR), a compound purified from Cortidis rhizoma, reduces serum cholesterol, triglycerides, and LDL-cholesterol of hypercholesterolemic patients and high fat diet fed animals, and increases hepatic LDLR mRNA and protein levels through a post-transcriptional mechanism. BBR also enhances the hypoglycemic action of insulin in diabetic animal models. Here, we show that BBR inhibits the differentiation of 3T3-L1 preadipocytes induced by DM and suppresses the mitotic clonal expansion of 3T3-L1 preadipocytes in a time- and dose-dependent manner. Gene expression analysis and Western blot analysis reveal that the BBR inhibits the mRNA and protein levels of adipogenesis related transcription factors PPARgamma and C/EBPalpha and their upstream regulator, C/EBPbeta. Reporter gene assays demonstrate that the full-length PPARgamma and alpha transcription activities are inhibited by BBR. Using real-time PCR, we have also found that the PPAR target genes that are involved in adipocyte differentiation, such as aP2, CD36, ACO, LPL, and other adipocyte markers, are suppressed by BBR. These studies suggest that BBR works on multiple molecular targets as an inhibitor of PPARgamma and alpha, and is a potential weight reducing, hypolipidemic, and hypoglycemic drug.
Huang
Cheng
C
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of CAS, Chinese Academy of Sciences, 294 Tai Yuan Road, Shanghai 200031, China.
Zhang
Yuebo
Y
Gong
Zhenwei
Z
Sheng
Xiaoyan
X
Li
Zongmeng
Z
Zhang
Wei
W
Qin
Ying
Y
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000187:drug effects; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D020869:Gene Expression Profiling; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D047493:PPAR alpha / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D014157:Transcription Factors; D001599:Berberine; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine