Effects of phorbol ester-sensitive PKC (c/nPKC) activation on the production of adiponectin in 3T3-L1 adipocytes.

Abstract

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.

• Authors: Takahide Ikeda, Kazuo Kajita, Wu Zhiliang, Takayuki Hanamoto, Ichiro Mori, Kei Fujioka, Hideyuki Okada, Takatoshi Fujikake, Yoshihiro Uno, Hiroyuki Morita, Isao Nagano, Yuzo Takahashi, Tatsuo Ishizuka
• Journal: IUBMB life (IUBMB Life) Vol. 61 Issue 6 Pg. 644-50 (Jun 2009) ISSN: 1521-6551 [Electronic] England
• PMID: 19472186 (Publication Type: Journal Article)
• Copyright: (c) 2009 IUBMB.

Chemical References

• Adiponectin
• Benzimidazoles
• Biphenyl Compounds
• Carbazoles
• Chromones
• Insulin
• Morpholines
• NF-kappa B
• PPAR gamma
• Tetrazoles
• Tumor Necrosis Factor-alpha
• Angiotensin II
• Go 6976
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Protein Kinase C
• Glucose
• Tetradecanoylphorbol Acetate
• candesartan

Topics

• 3T3-L1 Cells
• Adipocytes (metabolism)
• Adiponectin (biosynthesis)
• Angiotensin II (pharmacology)
• Animals
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Carbazoles (pharmacology)
• Chromones (pharmacology)
• Enzyme Activation
• Gene Expression (drug effects)
• Glucose (administration & dosage, pharmacology)
• Insulin (pharmacology)
• Mice
• Morpholines (pharmacology)
• NF-kappa B (drug effects, metabolism)
• PPAR gamma (physiology)
• Protein Kinase C (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tetrazoles (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)