Effects of phorbol ester-sensitive PKC (c/nPKC) activation on the production of adiponectin in 3T3-L1 adipocytes.
PPARgamma plays a key role in adipocyte specific gene expression. In this study, we assessed the effects of phorbol ester (TPA)-sensitive PKC (c/nPKC) activation on the expression of adipocyte specific genes and inflammation related genes. Treatment with both TPA and TNFalpha decreased mRNA levels of PPARgamma, aP2, LPL and adiponectin. TNFalpha, but not TPA, increased IL-6 and MCP-1 mRNA levels, Next, we investigated the effects of ligands which activate c/nPKC. Insulin and angiotensin II (AII), but not high glucose, reduced PPARgamma, aP2 and adiponectin mRNA levels. AII-induced suppression of these genes was restored in the presence of Go6976, a specific c/nPKC inhibitor, and candesartan, an AII receptor blocker. The effect of reduced insulin was prevented by Go6976 and LY294002, a specific PI 3-kinase inhibitors. Our results indicate that activation of c/nPKC could debilitate and/or might deteriorate insulin sensitivity in vivo, through the reduction of PPARgamma and adiponectin expression in adipocyte.
Ikeda
Takahide
T
Department of General Internal Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Kajita
Kazuo
K
Zhiliang
Wu
W
Hanamoto
Takayuki
T
Mori
Ichiro
I
Fujioka
Kei
K
Okada
Hideyuki
H
Fujikake
Takatoshi
T
Uno
Yoshihiro
Y
Morita
Hiroyuki
H
Nagano
Isao
I
Takahashi
Yuzo
Y
Ishizuka
Tatsuo
T
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D052242:Adiponectin / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002227:Carbazoles / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D052242:Adiponectin; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002227:Carbazoles; D002867:Chromones; D007328:Insulin; D009025:Morpholines; D016328:NF-kappa B; D047495:PPAR gamma; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; C081021:Go 6976; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; C081643:candesartan