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α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions.

Taher M, Mohamed Amiroudine MZ, Tengku Zakaria TM, Susanti D, Ichwan SJ, Kaderi MA, Ahmed QU, Zakaria ZA - Evid Based Complement Alternat Med (2015)

Bottom Line: Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells.Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM.The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Istana, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia.

ABSTRACT
Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.

No MeSH data available.


Related in: MedlinePlus

The effects of different concentration of α-mangostin (10, 25, 50 μM) in glucose uptake of 3T3-L1 adipocytes. Data is represented as mean ± SD, with n = 3 per group. *P < 0.05 compared to control group (DMSO treated cells), a = significant at indicated concentration.
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fig4: The effects of different concentration of α-mangostin (10, 25, 50 μM) in glucose uptake of 3T3-L1 adipocytes. Data is represented as mean ± SD, with n = 3 per group. *P < 0.05 compared to control group (DMSO treated cells), a = significant at indicated concentration.

Mentions: As PPARγ ligands can affect the adipocyte differentiation and are reported to have an effect on glucose uptake in 3T3-L1 adipocytes [44], hence, the next part of this study was designed to evaluate the effect of α-mangostin on the glucose uptake and insulin sensitivity. To determine 2-deoxy-D-glucose (2-DG) uptake stimulation by 3T3-L1 adipocytes, mature 3T3-L1 adipocytes were treated with α-mangostin at the indicated concentrations (10, 25, and 50 μM) for 60 min, and then glucose uptake activity was assessed. The cells were treated with metformin (1 mM) and sodium orthovanadate (5 mM) as positive controls, and undifferentiated DMSO treated cells were used as a negative control for the assay. The results indicated that the α-mangostin stimulated the glucose uptake in 3T3-L1 adipocytes. However, the insulin-induced glucose uptake was decreased by α-mangostin at 50 μM. This finding was interesting since the test compound also reduced lipid formation at the same dose for up to 44.4% compared to the MDI-treated cells. This raised our attention to further evaluate the mechanism of related mRNA expression. Figure 4 illustrates the insulin-stimulated glucose uptake by the compounds. Levels of radioactivity in the cell lysates were determined using a liquid scintillation counter.


α-Mangostin Improves Glucose Uptake and Inhibits Adipocytes Differentiation in 3T3-L1 Cells via PPARγ, GLUT4, and Leptin Expressions.

Taher M, Mohamed Amiroudine MZ, Tengku Zakaria TM, Susanti D, Ichwan SJ, Kaderi MA, Ahmed QU, Zakaria ZA - Evid Based Complement Alternat Med (2015)

The effects of different concentration of α-mangostin (10, 25, 50 μM) in glucose uptake of 3T3-L1 adipocytes. Data is represented as mean ± SD, with n = 3 per group. *P < 0.05 compared to control group (DMSO treated cells), a = significant at indicated concentration.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4385643&req=5

fig4: The effects of different concentration of α-mangostin (10, 25, 50 μM) in glucose uptake of 3T3-L1 adipocytes. Data is represented as mean ± SD, with n = 3 per group. *P < 0.05 compared to control group (DMSO treated cells), a = significant at indicated concentration.
Mentions: As PPARγ ligands can affect the adipocyte differentiation and are reported to have an effect on glucose uptake in 3T3-L1 adipocytes [44], hence, the next part of this study was designed to evaluate the effect of α-mangostin on the glucose uptake and insulin sensitivity. To determine 2-deoxy-D-glucose (2-DG) uptake stimulation by 3T3-L1 adipocytes, mature 3T3-L1 adipocytes were treated with α-mangostin at the indicated concentrations (10, 25, and 50 μM) for 60 min, and then glucose uptake activity was assessed. The cells were treated with metformin (1 mM) and sodium orthovanadate (5 mM) as positive controls, and undifferentiated DMSO treated cells were used as a negative control for the assay. The results indicated that the α-mangostin stimulated the glucose uptake in 3T3-L1 adipocytes. However, the insulin-induced glucose uptake was decreased by α-mangostin at 50 μM. This finding was interesting since the test compound also reduced lipid formation at the same dose for up to 44.4% compared to the MDI-treated cells. This raised our attention to further evaluate the mechanism of related mRNA expression. Figure 4 illustrates the insulin-stimulated glucose uptake by the compounds. Levels of radioactivity in the cell lysates were determined using a liquid scintillation counter.

Bottom Line: Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells.Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM.The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Jalan Istana, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia.

ABSTRACT
Obesity has been often associated with the occurrence of cardiovascular diseases, type 2 diabetes, and cancer. The development of obesity is also accompanied by significant differentiation of preadipocytes into adipocytes. In this study, we investigated the activity of α-mangostin, a major xanthone component isolated from the stem bark of G. malaccensis, on glucose uptake and adipocyte differentiation of 3T3-L1 cells focusing on PPARγ, GLUT4, and leptin expressions. α-Mangostin was found to inhibit cytoplasmic lipid accumulation and adipogenic differentiation. Cells treated with 50 μM of α-mangostin reduced intracellular fat accumulation dose-dependently up to 44.4% relative to MDI-treated cells. Analyses of 2-deoxy-D-[(3)H] glucose uptake activity showed that α-mangostin significantly improved the glucose uptake (P < 0.05) with highest activity found at 25 μM. In addition, α-mangostin increased the amount of free fatty acids (FFA) released. The highest glycerol release level was observed at 50 μM of α-mangostin. qRT-PCR analysis showed reduced lipid accumulation via inhibition of PPARγ gene expression. Induction of glucose uptake and free fatty acid release by α-mangostin were accompanied by increasing mRNA expression of GLUT4 and leptin. These evidences propose that α-mangostin might be possible candidate for the effective management of obesity in future.

No MeSH data available.


Related in: MedlinePlus