Thiazolidinedione- and tumor necrosis factor alpha-induced downregulation of peroxisome proliferator-activated receptor gamma mRNA in differentiated 3T3-L1 adipocytes.
Thiazolidinediones (TZDs) are antidiabetic insulin-sensitizing agents that bind to peroxisome proliferator-activated receptor gamma (PPARgamma) and have potent adipogenic effects on 3T3-L1 preadipocytes. In fully differentiated 3T3-L1 adipocytes, TZDs markedly decreased PPARgamma mRNA levels without reducing the expression of genes that are positively regulated by PPARgamma, such as adipocyte lipid-binding protein 2 (aP2) or lipoprotein lipase-(LPL). PPARgamma mRNA levels were also downregulated by tumor necrosis factor alpha (TNFalpha), an antiadipogenic cytokine. We propose that the downregulation of PPARgamma is not the common denominator of the metabolic effects of TZDs and TNFalpha on mature adipocytes.
Perrey
S
S
Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Japan.
Ishibashi
S
S
Yahagi
N
N
Osuga
J
J
Tozawa
R
R
Yagyu
H
H
Ohashi
K
K
Gotoda
T
T
Harada
K
K
Chen
Z
Z
Iizuka
Y
Y
Shionoiri
F
F
Yamada
N
N
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C089946:2,4-thiazolidinedione