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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

The effect of MG on 3T3-L1 cell proliferation, GSH level and glyoxalase I activity.The relative cell proliferation of each group was presented as the ratio between arbitrary absorbance on 570 nm of each group and that from the control group without treatment. The effect of different MG concentrations on cell proliferation was shown in (A) and the effect of 10 µM MG with/without SH-6 and alagebrium was shown in (B). The reduced GSH level (C ) and unchanged glyoxalase I activity (D) was observed in 3T3-L1 cells treated with 5, 10, 20 and 50 µM MG. *P<0.05, **P<0.01 vs control cells; +P<0.05 vs MG treated cells; n = 12 in each group.
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pone-0036610-g002: The effect of MG on 3T3-L1 cell proliferation, GSH level and glyoxalase I activity.The relative cell proliferation of each group was presented as the ratio between arbitrary absorbance on 570 nm of each group and that from the control group without treatment. The effect of different MG concentrations on cell proliferation was shown in (A) and the effect of 10 µM MG with/without SH-6 and alagebrium was shown in (B). The reduced GSH level (C ) and unchanged glyoxalase I activity (D) was observed in 3T3-L1 cells treated with 5, 10, 20 and 50 µM MG. *P<0.05, **P<0.01 vs control cells; +P<0.05 vs MG treated cells; n = 12 in each group.

Mentions: To investigate whether MG treatment could induce the proliferation of 3T3-L1 cells, we carried out a cell proliferation assay with or without MG treatment (1.25∼50 µM). MG at 5, 10 and 20 µM increased the proliferation rate of 3T3-L1 cells to 115±2.1%, 126±3.6% and 119±3.3% of the untreated cells (P<0.05 vs. control; n = 48 in each group, Fig. 2A). The co-treatment with Akt inhibitor SH-6 (10 µM) or the AGE lowering reagent alagebrium (50 µM) prevented the MG-induced cell proliferation (Fig. 2B). When 3T3-L1 cells were treated with MG (5∼50 µM), the GSH level was significantly decreased. Consistent with the results from animal study, gloxalase I activity were not significantly altered by MG treatment (Fig. 2C, D).


Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.

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

The effect of MG on 3T3-L1 cell proliferation, GSH level and glyoxalase I activity.The relative cell proliferation of each group was presented as the ratio between arbitrary absorbance on 570 nm of each group and that from the control group without treatment. The effect of different MG concentrations on cell proliferation was shown in (A) and the effect of 10 µM MG with/without SH-6 and alagebrium was shown in (B). The reduced GSH level (C ) and unchanged glyoxalase I activity (D) was observed in 3T3-L1 cells treated with 5, 10, 20 and 50 µM MG. *P<0.05, **P<0.01 vs control cells; +P<0.05 vs MG treated cells; n = 12 in each group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0036610-g002: The effect of MG on 3T3-L1 cell proliferation, GSH level and glyoxalase I activity.The relative cell proliferation of each group was presented as the ratio between arbitrary absorbance on 570 nm of each group and that from the control group without treatment. The effect of different MG concentrations on cell proliferation was shown in (A) and the effect of 10 µM MG with/without SH-6 and alagebrium was shown in (B). The reduced GSH level (C ) and unchanged glyoxalase I activity (D) was observed in 3T3-L1 cells treated with 5, 10, 20 and 50 µM MG. *P<0.05, **P<0.01 vs control cells; +P<0.05 vs MG treated cells; n = 12 in each group.
Mentions: To investigate whether MG treatment could induce the proliferation of 3T3-L1 cells, we carried out a cell proliferation assay with or without MG treatment (1.25∼50 µM). MG at 5, 10 and 20 µM increased the proliferation rate of 3T3-L1 cells to 115±2.1%, 126±3.6% and 119±3.3% of the untreated cells (P<0.05 vs. control; n = 48 in each group, Fig. 2A). The co-treatment with Akt inhibitor SH-6 (10 µM) or the AGE lowering reagent alagebrium (50 µM) prevented the MG-induced cell proliferation (Fig. 2B). When 3T3-L1 cells were treated with MG (5∼50 µM), the GSH level was significantly decreased. Consistent with the results from animal study, gloxalase I activity were not significantly altered by MG treatment (Fig. 2C, D).

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