Alpha-lipoic acid inhibits adipocyte differentiation by regulating pro-adipogenic transcription factors via mitogen-activated protein kinase pathways.
Obesity is associated with a number of pathological disorders such as non-insulin-dependent diabetes, hypertension, hyperlipidemia, and cardiovascular diseases. alpha-Lipoic acid (LA) has been demonstrated to activate the insulin signaling pathway and to exert insulin-like actions in adipose and muscle cells. Based on this similarity LA is expected to promote adipogenesis in pre-adipocytes. Here, however, we report that LA inhibited differentiation of 3T3-L1 pre-adipocytes induced by a hormonal mixture or troglitazone. Northern blot analysis of cells demonstrated that this inhibition was accompanied with attenuated expression of adipocyte-specific fatty acid-binding protein and lipoprotein lipase. Electrophoretic mobility shift assay and Western blot analysis of cells demonstrated that LA modulates transcriptional activity and/or expression of a set of anti- or pro-adipogenic transcription factors. LA treatment of 3T3-L1 pre-adipocytes also resulted in prolonged activation of major mitogen-activated protein kinase signaling pathways but showed little or no effect on the activity of the insulin receptor/Akt signaling pathway. These findings suggest that LA inhibits insulin or the hormonal mixture-induced differentiation of 3T3-L1 pre-adipocytes by modulating activity and/or expression of pro- or anti-adipogenic transcription factors mainly through activating the MAPK pathways.
Cho
Kyung-Joo
KJ
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Moon
Hae-Eun
HE
Moini
Hadi
H
Packer
Lester
L
Yoon
Do-Young
DY
Chung
An-Sik
AS
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D008063:Thioctic Acid / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone
D002839:Chromans; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D008063:Thioctic Acid; D008071:Lipoprotein Lipase; D000077288:Troglitazone; D013936:Thymidine