|ZHAO, LING - University Of Tennessee|
|HU, PAN - University Of Tennessee|
|ZHOU, YIJUN - University Of Tennessee|
|PUROHIT, JAANKI - University Of Tennessee|
Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/16/2011
Publication Date: 6/21/2011
Citation: Zhao, L., Hu, P., Zhou, Y., Purohit, J., Hwang, D.H. 2011. NOD1 activation induces proinflammatory gene expression and insulin resistance in 3T3-L1 adipocytes. American Journal of Physiology. Available: http://ajpendo.physiology.org/content/early/2011/06/15/ajpendo.00709.2010.reprint
Interpretive Summary: Nucleotide binding oligomerization domain containing protein 1 (NOD1) is a cytosolic pattern recognition receptor that can be modulated by dietary fatty acids and phytochemicals. We found that activation of NOD1 impairs insulin signaling and glucose uptake in 3T3-L1 adipocytes. These results suggest that modulation of insulin resistance in adipocytes by dietary fatty acids is at least in part mediated by NOD1 protein.
Technical Abstract: Chronic inflammation is associated with obesity and insulin resistance. However, the underlying mechanisms are not fully understood. Pattern recognition receptors Toll-like receptors and Nucleotide-oligomerization domain containing proteins play critical roles in innate immune response. Here we report that activation of nucleotide binding oligomerization domain containing protein 1 (NOD1) in adipocytes impairs insulin signaling and glucose uptake. The mRNA level of NOD1 is markedly increased in differentiated murine 3T3-L1 adipocytes and human primary adipocyte culture upon adipocyte conversion. Stimulation of NOD1 with a synthetic ligand Tri-DAP induces proinflammatory chemokine MCP-1, RANTES and cytokine TNF-a and MIP-2 (human IL-8 homolog) and IL-6 mRNA expression in 3T3-L1 adipocytes in a time and dose dependent manner. Similar proinflammatory profiles are observed in human primary adipocyte culture stimulated with Tri-DAP. Moreover, NOD1 activation suppresses insulin signaling as revealed by attenuated phosphorylation of Akt and downstream target GSK3a/3ß and subsequent insulin-induced glucose uptake in 3T3-L1 adipocytes. Together, our results suggest that NOD1 may play an important role in adipose inflammation and insulin resistance.