The effects of AICAR on adipocyte differentiation of 3T3-L1 cells.
The AMP-activated protein kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), has been found to inhibit the differentiation of 3T3-L1 adipocytes, if added at an early phase of differentiation. AICAR blocks the expression of the late adipogenic markers, fatty acid synthase and acetyl-CoA carboxylase, and of the transcription factors, C/EBPalpha and PPARgamma. It also inhibits early clonal expansion of pre-adipocytes, prevents the fall in C/EBPbeta expression during the intermediate stage of differentiation and inhibits the late phase expression of CHOP-10, an antagonist of C/EBPbeta. These data suggest a possible inhibitory role for AMPK in the process of adipose differentiation and suggest that AMPK might be a target to block adipogenesis.
Habinowski
S A
SA
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Witters
L A
LA
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D012265:Ribonucleotides / Q000494:pharmacology*; D013997:Time Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000096:biosynthesis
D001391:Azo Compounds; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497250:Ddit3 protein, mouse; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D012265:Ribonucleotides; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; C011049:oil red O