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Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.

Jia X, Chang T, Wilson TW, Wu L - PLoS ONE (2012)

Bottom Line: The effects of MG on diabetes and hypertension have been long recognized.The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells.The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Collage of Medicine, University of Saskatchewan, Saskatoon, Canada.

ABSTRACT
Methylglyoxal (MG) is a highly reactive metabolite physiologically presented in all biological systems. The effects of MG on diabetes and hypertension have been long recognized. In the present study, we investigated the potential role of MG in obesity, one of the most important factors to cause metabolic syndrome. An increased MG accumulation was observed in the adipose tissue of obese Zucker rats. Cell proliferation assay showed that 5-20 µM of MG stimulated the proliferation of 3T3-L1 cells. Further study suggested that accumulated-MG stimulated the phosphorylation of Akt1 and its targets including p21 and p27. The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells. The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6. In summary, our study revealed a previously unrecognized effect of MG in stimulating adipogenesis by up-regulation of Akt signaling pathway and this mechanism might offer a new approach to explain the development of obesity.

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Related in: MedlinePlus

Effect of MG on Akt1 phosphorylation in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of Akt1, (A), Representive Western blot of phospho-Akt1 (p-Akt1(Ser473), p-Akt1(thr308)) and Akt1; (B), The level of phospho-Akt1(Ser473) in 3T3-L1 cells with/without MG treatment; (C ), The level of phospho-Akt1(thr308) in 3T3-L1 cells with/without MG treatment. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments. CT: control; ALA: alagebrium.
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pone-0036610-g004: Effect of MG on Akt1 phosphorylation in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of Akt1, (A), Representive Western blot of phospho-Akt1 (p-Akt1(Ser473), p-Akt1(thr308)) and Akt1; (B), The level of phospho-Akt1(Ser473) in 3T3-L1 cells with/without MG treatment; (C ), The level of phospho-Akt1(thr308) in 3T3-L1 cells with/without MG treatment. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments. CT: control; ALA: alagebrium.

Mentions: To further understand the mechanism of MG induced cell proliferation in 3T3-L1 cells, the phosphorylation of Akt1 isoform was studied in cultured cells. Consistent with our observations of Akt1 in Zucker obese and lean animals, the levels of phospho-Akt1(Ser473) and phospho-Akt1(Thr308) in cultured 3T3-L1 cells were significantly increased after MG treatment (10 and 30 µM) for 24 h (Fig. 4). Co-application of alagebrium (50 µM) with MG attenuated the phosphorylation levels on both Ser473 and Thr308 of Akt1. Alagebrium itself had no significant effect on phospho-Akt1.


Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.

Jia X, Chang T, Wilson TW, Wu L - PLoS ONE (2012)

Effect of MG on Akt1 phosphorylation in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of Akt1, (A), Representive Western blot of phospho-Akt1 (p-Akt1(Ser473), p-Akt1(thr308)) and Akt1; (B), The level of phospho-Akt1(Ser473) in 3T3-L1 cells with/without MG treatment; (C ), The level of phospho-Akt1(thr308) in 3T3-L1 cells with/without MG treatment. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments. CT: control; ALA: alagebrium.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351465&req=5

pone-0036610-g004: Effect of MG on Akt1 phosphorylation in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of Akt1, (A), Representive Western blot of phospho-Akt1 (p-Akt1(Ser473), p-Akt1(thr308)) and Akt1; (B), The level of phospho-Akt1(Ser473) in 3T3-L1 cells with/without MG treatment; (C ), The level of phospho-Akt1(thr308) in 3T3-L1 cells with/without MG treatment. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments. CT: control; ALA: alagebrium.
Mentions: To further understand the mechanism of MG induced cell proliferation in 3T3-L1 cells, the phosphorylation of Akt1 isoform was studied in cultured cells. Consistent with our observations of Akt1 in Zucker obese and lean animals, the levels of phospho-Akt1(Ser473) and phospho-Akt1(Thr308) in cultured 3T3-L1 cells were significantly increased after MG treatment (10 and 30 µM) for 24 h (Fig. 4). Co-application of alagebrium (50 µM) with MG attenuated the phosphorylation levels on both Ser473 and Thr308 of Akt1. Alagebrium itself had no significant effect on phospho-Akt1.

Bottom Line: The effects of MG on diabetes and hypertension have been long recognized.The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells.The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Collage of Medicine, University of Saskatchewan, Saskatoon, Canada.

ABSTRACT
Methylglyoxal (MG) is a highly reactive metabolite physiologically presented in all biological systems. The effects of MG on diabetes and hypertension have been long recognized. In the present study, we investigated the potential role of MG in obesity, one of the most important factors to cause metabolic syndrome. An increased MG accumulation was observed in the adipose tissue of obese Zucker rats. Cell proliferation assay showed that 5-20 µM of MG stimulated the proliferation of 3T3-L1 cells. Further study suggested that accumulated-MG stimulated the phosphorylation of Akt1 and its targets including p21 and p27. The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells. The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6. In summary, our study revealed a previously unrecognized effect of MG in stimulating adipogenesis by up-regulation of Akt signaling pathway and this mechanism might offer a new approach to explain the development of obesity.

Show MeSH
Related in: MedlinePlus