title: Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.
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.
authors.affiliation: Department of Pharmacology, Collage of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: Xuming
authors.initials: X
authors.lastname: Jia
authors.forename: Tuanjie
authors.initials: T
authors.lastname: Chang
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wilson
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D018797:Cell Cycle Proteins; D011765:Pyruvaldehyde; C514862:Akt1 protein, mouse; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D007791:Lactoylglutathione Lyase; D005978:Glutathione