CCR4-NOT2 Promotes the Differentiation and Lipogenesis of 3T3-L1 Adipocytes via Upregulation of PPARx03B3;, CEBPα and Inhibition of P-GSK3α/β and β-Catenin.

Abstract

BACKGROUND/AIMS:

Though CCR4-NOT2 (CNOT2), one of CCR4-NOT complex subunits, was known to be involved in metastasis and apoptosis through transcription and mRNA degradation, its other biological function is poorly understood so far. The aim of this study is to elucidate the molecular role of CNOT2 in the differentiation process of 3T3-L1 preadipocytes.

METHODS AND RESULTS:

CNOT2 was overexpressed during the differentiation process of 3T3-L1 preadipocytes. Consistently, mRNA levels of CNOT2, adiponectin, adiponectin 2, PPARx03B3; and CEBPα were enhanced in 3T3-L1 adipocytes. Conversely, CNOT2 depletion by siRNA transfection also reversed the activation of PPARx03B3; and CEBPα and inhibition of GSK3α/β and β-catenin at the protein level in 3T3-L1 preadipocytes. Immunofluorescence assay revealed that CNOT2 was colocalized with PPARx03B3;, but not with CEBPα in 3T3-L1 adipocyte. Consistently, IP western blots revealed that CNOT2 interacted with PPARx03B3; in 3T3-L1 adipocyte.

CONCLUSION:

Our findings demonstrate that CNOT2 promotes the differentiation of 3T3-L1 preadipocytes via upregulation of PPARx03B3;, and CEBPα and inhibition of GSK3α/β and β-catenin signaling as a potent molecular target for obesity.

• Authors: Eun Jung Sohn, Deok-Beom Jung, Jihyun Lee, Sang Wook Yoon, Gun-Ho Won, Hyun Suk Ko, Sung-Hoon Kim
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 37 Issue 5 Pg. 1881-9 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26584287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Adiponectin
• CCAAT-Enhancer-Binding Proteins
• CEBPA protein, mouse
• PPAR gamma
• RNA, Messenger
• RNA, Small Interfering
• Repressor Proteins
• beta Catenin
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• glycogen synthase kinase 3 alpha

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, metabolism)
• Adipogenesis
• Adiponectin (genetics, metabolism)
• Animals
• CCAAT-Enhancer-Binding Proteins (genetics, metabolism)
• Down-Regulation
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Mice
• Microscopy, Fluorescence
• PPAR gamma (genetics, metabolism)
• Phosphorylation
• RNA Interference
• RNA, Messenger (metabolism)
• RNA, Small Interfering (metabolism)
• Repressor Proteins (antagonists & inhibitors, genetics, metabolism)
• Up-Regulation
• beta Catenin (metabolism)