title: Methotrexate enhances 3T3-L1 adipocytes hypertrophy.
abstract: Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and (3)H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. (3)H-Deoxyglucose ((3)H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and (3)H-thymidine incorporation (P < 0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal (3)H-DG uptake by adipocytes (P < 0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of (3)H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX.
authors: Departamento de Bioquímica (U38-FCT), Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Oporto, Portugal. csmarques@med.up.pt
authors: Cláudia
authors: C
authors: Marques
authors: Diana
authors: D
authors: Teixeira
authors: Ana
authors: A
authors: Cunha
authors: Manuela
authors: M
authors: Meireles
authors: Diogo
authors: D
authors: Pestana
authors: Elisa
authors: E
authors: Keating
authors: Conceição
authors: C
authors: Calhau
authors: Rosário
authors: R
authors: Monteiro
authors: Ana
authors: A
authors: Faria
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D009765:Obesity / Q000150:complications
chemical_list: D005493:Folic Acid Antagonists; D007328:Insulin; D005947:Glucose; D008727:Methotrexate