Fructose promotes the differentiation of 3T3-L1 adipocytes and accelerates lipid metabolism

• Published in: FEBS letters 2014-01, Vol.588 (3), p.490-496
• Main Authors: Legeza, Balázs, Balázs, Zoltán, Odermatt, Alex
• Format: Article
• Language: English
• Subjects: 11-beta-Hydroxysteroid Dehydrogenases - biosynthesis; 11β-HSD; 11β-hydroxysteroid dehydrogenase; 11β-hydroxysteroid dehydrogensae; 3T3-L1 Cells; Adipocyte; adipocyte triglyceride lipase; Adipocytes - cytology; Adipocytes - drug effects; Animals; ATGL; C/EBPα; CCAT/enhancer-binding protein α; Cell Differentiation - drug effects; DMEM; Dulbecco's modified Eagles medium; Endoplasmic Reticulum; F6P; Fatty Acid-Binding Proteins - biosynthesis; FBS; fetal bovine serum; FFA; Fibroblasts - cytology; Fibroblasts - drug effects; free fatty acids; Fructose; Fructose - metabolism; Fructose - pharmacology; fructose-6-phosphate; Gene Expression Regulation, Enzymologic; Glucocorticoid; Glucose; glucose transporter 5; GLUT5; H6PDH; HEK293 Cells; hexose-6-phosphate dehydrogenase; hormone sensitive lipase; HPRT; HSL; Humans; hypoxanthine-guanine phosphoribosyltransferase; Lipid Metabolism - drug effects; Lipolysis; Metabolic syndrome; Metabolism; Mice; peroxisome proliferator-activated receptor γ; PPARγ; thin layer chromatography; TLC
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.12.014

•Fructose is a potent adipocyte differentiation agent.•Fructose stimulates NADPH generation in the endoplasmic reticulum.•Fructose enhances glucocorticoid activation in adipocytes.•Enhanced glucocorticoid activation increases lipolysis. Excessive fructose consumption and elevated glucocorticoids contribute to metabolic syndrome. We show that fructose as the only carbohydrate source is sufficient for the differentiation of 3T3-L1 fibroblasts into adipocytes. Differentiation of cells in fructose containing medium resulted in increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression and activity. Experiments with transfected HEK-293 cells suggested more efficient NADPH generation by fructose compared with glucose in the endoplasmic reticulum (ER). Adipocytes differentiated in the presence of fructose showed increased FABP4 expression, C/EBPα to C/EBPβ ratio and lipolysis. Thus, excessive fructose may cause adverse metabolic effects by enhancing 11β-HSD1 activity and increasing lipolysis in adipocytes.