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Suppression of Very Early Stage Of Adipogenesis by Baicalein, a Plant-Derived Flavonoid through Reduced Akt-C/EBP α -GLUT4 Signaling-Mediated Glucose Uptake in 3T3-L1 Adipocytes

View Article: PubMed Central - PubMed

ABSTRACT

Baicalein has been used as a Chinese medicine, and is an abundant plant flavonoid present in fruits and vegetables. Here, we examined the effects of baicalein in adipogenesis and investigated its molecular mechanism in adipocytes. Baicalein lowered the intracellular lipid accumulation and decreased the transcription levels of the adipocyte-specific genes in mouse 3T3-L1 adipocytes. Glucose uptake mediated by glucose transporter 4 (GLUT4) was reduced, causing down-regulation of the intracellular lipid accumulation. These reductions were also observed even when baicalein was added in only early stage of adipogenesis (0–2 days) of 6-day-adipogenesis. Chromatin immunoprecipitation assay showed that baicalein decreased the binding level of C/EBPα protein to the promoter region of the GLUT4 gene. Phosphorylation of Akt at 1 h after the initiation of adipogenesis was inhibited by the treatment with baicalein. Inhibition during only the first 1.5 h after the initiation of adipogenesis by baicalein or an Akt inhibitor was enough to decrease the lipid contents in the cells undergoing adipocyte differentiation for 6 days. These results indicate that baicalein decreased the intracellular lipid accumulation by down-regulation of glucose uptake via repression of Akt-C/EBPα-GLUT4 signaling in the very early stage of adipogenesis of 3T3-L1 adipocytes.

No MeSH data available.


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Decreased expression of adipogenesis-related genes by baicalein in early stage of adipogenesis.A, Expression levels of the adipogenic and lipogenic genes. 3T3-L1 cells (undifferentiated cells: U; white columns) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM in the absence (gray columns) or presence (50 μM; black columns) of baicalein during days 0–2 or 0–6. Data are presented as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets. B, Decrease in glucose uptake in 3T3-L1 cells by baicalein. Cells (undifferentiated cells: U) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM containing baicalein or not (0 or 50 μM) during days 0–2 or 0–6. Cells were further incubated with the fluorescent 2-NBDG, and then observed under a fluorescence microscope. C, Quantification of glucose uptake in baicalein-treated, differentiated 3T3-L1 cells. Cells were prepared as described in the legend of Fig 5B. The data are presented as the value relative to that of the undifferentiated cells and are shown as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets.
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pone.0163640.g005: Decreased expression of adipogenesis-related genes by baicalein in early stage of adipogenesis.A, Expression levels of the adipogenic and lipogenic genes. 3T3-L1 cells (undifferentiated cells: U; white columns) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM in the absence (gray columns) or presence (50 μM; black columns) of baicalein during days 0–2 or 0–6. Data are presented as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets. B, Decrease in glucose uptake in 3T3-L1 cells by baicalein. Cells (undifferentiated cells: U) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM containing baicalein or not (0 or 50 μM) during days 0–2 or 0–6. Cells were further incubated with the fluorescent 2-NBDG, and then observed under a fluorescence microscope. C, Quantification of glucose uptake in baicalein-treated, differentiated 3T3-L1 cells. Cells were prepared as described in the legend of Fig 5B. The data are presented as the value relative to that of the undifferentiated cells and are shown as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets.

Mentions: Next, we measured changes in the expression levels of the adipogenic and lipogenic genes in cells which were differentiating into adipocytes in medium containing baicalein or not during days 0–2, days 0–6 during the 6-day-adipogenesis. The transcription levels of the adipogenic PPARγ, C/EBPα, and aP2 genes and of the lipogenic ACC, FAS, and SCD genes were all decreased when the cells were treated with baicalein during days 0–2 of adipogenesis, which results were almost the same as those obtained when baicalein was present for all 6 days (Fig 5A) and the results obtained in medium containing baicalein during days 2–4 or days 4–6 during the 6-day-adipogenesis (data not shown).


Suppression of Very Early Stage Of Adipogenesis by Baicalein, a Plant-Derived Flavonoid through Reduced Akt-C/EBP α -GLUT4 Signaling-Mediated Glucose Uptake in 3T3-L1 Adipocytes
Decreased expression of adipogenesis-related genes by baicalein in early stage of adipogenesis.A, Expression levels of the adipogenic and lipogenic genes. 3T3-L1 cells (undifferentiated cells: U; white columns) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM in the absence (gray columns) or presence (50 μM; black columns) of baicalein during days 0–2 or 0–6. Data are presented as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets. B, Decrease in glucose uptake in 3T3-L1 cells by baicalein. Cells (undifferentiated cells: U) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM containing baicalein or not (0 or 50 μM) during days 0–2 or 0–6. Cells were further incubated with the fluorescent 2-NBDG, and then observed under a fluorescence microscope. C, Quantification of glucose uptake in baicalein-treated, differentiated 3T3-L1 cells. Cells were prepared as described in the legend of Fig 5B. The data are presented as the value relative to that of the undifferentiated cells and are shown as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036867&req=5

pone.0163640.g005: Decreased expression of adipogenesis-related genes by baicalein in early stage of adipogenesis.A, Expression levels of the adipogenic and lipogenic genes. 3T3-L1 cells (undifferentiated cells: U; white columns) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM in the absence (gray columns) or presence (50 μM; black columns) of baicalein during days 0–2 or 0–6. Data are presented as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets. B, Decrease in glucose uptake in 3T3-L1 cells by baicalein. Cells (undifferentiated cells: U) were differentiated into adipocytes (differentiated cells: D) for 6 days in DMEM containing baicalein or not (0 or 50 μM) during days 0–2 or 0–6. Cells were further incubated with the fluorescent 2-NBDG, and then observed under a fluorescence microscope. C, Quantification of glucose uptake in baicalein-treated, differentiated 3T3-L1 cells. Cells were prepared as described in the legend of Fig 5B. The data are presented as the value relative to that of the undifferentiated cells and are shown as the means ± S.D. from three experiments. **p<0.01, as indicated by the brackets.
Mentions: Next, we measured changes in the expression levels of the adipogenic and lipogenic genes in cells which were differentiating into adipocytes in medium containing baicalein or not during days 0–2, days 0–6 during the 6-day-adipogenesis. The transcription levels of the adipogenic PPARγ, C/EBPα, and aP2 genes and of the lipogenic ACC, FAS, and SCD genes were all decreased when the cells were treated with baicalein during days 0–2 of adipogenesis, which results were almost the same as those obtained when baicalein was present for all 6 days (Fig 5A) and the results obtained in medium containing baicalein during days 2–4 or days 4–6 during the 6-day-adipogenesis (data not shown).

View Article: PubMed Central - PubMed

ABSTRACT

Baicalein has been used as a Chinese medicine, and is an abundant plant flavonoid present in fruits and vegetables. Here, we examined the effects of baicalein in adipogenesis and investigated its molecular mechanism in adipocytes. Baicalein lowered the intracellular lipid accumulation and decreased the transcription levels of the adipocyte-specific genes in mouse 3T3-L1 adipocytes. Glucose uptake mediated by glucose transporter 4 (GLUT4) was reduced, causing down-regulation of the intracellular lipid accumulation. These reductions were also observed even when baicalein was added in only early stage of adipogenesis (0&ndash;2 days) of 6-day-adipogenesis. Chromatin immunoprecipitation assay showed that baicalein decreased the binding level of C/EBP&alpha; protein to the promoter region of the GLUT4 gene. Phosphorylation of Akt at 1 h after the initiation of adipogenesis was inhibited by the treatment with baicalein. Inhibition during only the first 1.5 h after the initiation of adipogenesis by baicalein or an Akt inhibitor was enough to decrease the lipid contents in the cells undergoing adipocyte differentiation for 6 days. These results indicate that baicalein decreased the intracellular lipid accumulation by down-regulation of glucose uptake via repression of Akt-C/EBP&alpha;-GLUT4 signaling in the very early stage of adipogenesis of 3T3-L1 adipocytes.

No MeSH data available.


Related in: MedlinePlus