The inhibitory effects of PKCθ on adiponectin expression is mediated by ERK in 3T3-L1 adipocytes.

Abstract

The research suggests that adiponectin plays an important role in sensitizing insulin action. It is interesting to find that the lower levels of adiponectin exist in the plasma of obese and Type 2 diabetes subjects and in the adipose tissue of obese, db/db mice, and insulin-resistant individuals. However, the underlying mechanism by which adiponectin expression is inhibited remains largely unknown. In this study, we reported that adipogenesis was inhibited by the stable over-expression of protein kinase C θ (PKCθ) in 3T3-L1 pre - adipocytes. The prolonged treatment of mature 3T3-L1 adipocytes with palmitate, a kind of saturated free fatty acid, reduced adiponectin expression at both mRNA level and protein level, accompanied with the enhanced phosphorylation of PKCθ and extracellular signal-regulated kinase (ERK), and the impaired expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) mRNA. Either PD98059, an ERK inhibitor or PKCθ pseudosubstrate, a specific PKCθ inhibitor, restored palmiate-inhibited PPARγ2 mRNA expression and subsequent adiponectin expression. In addition, the over-expression or activation of PKCθ resulted in the enhanced phosphorylation of ERK in the mature 3T3-L1 adipocytes. PKCθ pseudosubstrate significantly reduced the phorbol 3-myristate 12-acetate (PMA)-induced phosphorylation of ERK. The data suggested that PKCθ-dependent activity of ERK resulted in the impaired expression of PPARγ2 mRNA leading to the reduction of adiponectin expression in the mature 3T3-L1 adipocytes.

• Authors: S Sun, Y Liu, J Lu, A Omar, S Sun, Y Bi, C Wang
• Journal: Journal of endocrinological investigation (J Endocrinol Invest) Vol. 34 Issue 1 Pg. 8-15 (Jan 2011) ISSN: 1720-8386 [Electronic] Italy
• PMID: 20339310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Adipoq protein, mouse
• Isoenzymes
• PPAR gamma
• Prkcq protein, mouse
• Protein Kinase C
• Protein Kinase C-theta
• Extracellular Signal-Regulated MAP Kinases

Topics

• 3T3-L1 Cells
• Adipocytes (metabolism, physiology)
• Adipogenesis (genetics, physiology)
• Adiponectin (genetics, metabolism)
• Animals
• Cell Differentiation (genetics)
• Down-Regulation (physiology)
• Extracellular Signal-Regulated MAP Kinases (metabolism, physiology)
• Gene Expression Regulation
• Isoenzymes (genetics, metabolism, physiology)
• MAP Kinase Signaling System (physiology)
• Mice
• PPAR gamma (genetics, metabolism, physiology)
• Protein Kinase C (genetics, metabolism, physiology)
• Protein Kinase C-theta
• Transfection