A Negative Regulatory Pathway of GLUT4 Trafficking in Adipocyte: New Function of RIP140 in the Cytoplasm via AS160

作者：Ho, Ping-Chih; Lin, Yi-Wei; Tsui, Yao-Chen; Gupta, Pawan; Wei, Li-Na

来源：Cell Metabolism, 2009, 10(6): 516-523.

DOI：10.1016/j.cmet.2009.09.012

• TRANSCRIPTIONAL COREPRESSOR RIP140
• FATTY LIVER-DISEASE
• GLUCOSE-TRANSPORTER
• REPRESSIVE ACTIVITY
• INSULIN-RESISTANCE
• 3T3-L1 ADIPOCYTES
• OXIDATIVE-METABOLISM
• ARGININE METHYLATION
• GENE-REGULATION
• PHOSPHORYLATION

Receptor-interacting protein 140 (RIP140), a nuclear receptor corepressor, is important for lipid and glucose metabolism. In adipocytes, RIP140 can be phosphorylated by protein kinase C epsilon (PKC epsilon), followed by arginine methylation, and exported to the cytoplasm. This study demonstrates for the first time a cytoplasmic function for RIP140: to counteract insulin-stimulated glucose transporter 4 (GLUT4) membrane partitioning and glucose uptake in adipocytes. Cytoplasmic RIP140 interacts with the Akt substrate AS160, thereby impeding AS160 phosphorylation by Akt; this in turn reduces GLUT4 trafficking. This signal transduction pathway can be recapitulated in the epididymal adipocytes of diet-induced obese mice: nuclear PKC epsilon is activated, cytoplasmic RIP140 increases, and GLUT4 trafficking and glucose uptake are reduced. The data reveal a new, cytoplasmic function for RIP140 as a negative regulator of GLUT4 trafficking and glucose uptake, and shed insight into the regulation of basal and insulin-stimulated glucose disposal by a nuclear-initiated counteracting mechanism.

• 出版日期2009-12-2