NOD1 activation induces proinflammatory gene expression and insulin resistance in 3T3‐L1 adipocytes

Abstract

Chronic inflammation is associated with obesity and insulin resistance. However, the underlying mechanisms are not fully understood. Pattern recognition receptors (PRRs) play critical roles in innate immune response. Here we report a role of Nucleotide‐binding Oligomerization Domain protein 1 (NOD1), a member of PRR, in adipocyte inflammation and insulin resistance. mRNA level of NOD1 is increased by 4 fold in differentiated 3T3‐L1 adipocytes compared with preadipocytes. Stimulation of NOD1 with a synthetic ligand Tri‐DAP induces proinflammatory chemokine MCP‐1, RANTES and cytokine TNF‐α and MIP‐2 mRNA expression and protein secretion. Moreover, stimulation of NOD1 with Tri‐DAP suppresses insulin signaling as revealed by attenuated Akt phosphorylation on Ser 473 and Thr 308 and subsequent insulin‐induced glucose uptake in 3T3‐L1 adipocytes. In addition, NOD1 mRNA is also increased upon differentiation of primary culture derived from human fat. Stimulation of NOD1 induces similar proinflammatory chemokine/cytokine mRNA expression and protein secretion. Together, our results suggest that NOD1 may be involved in adipose inflammation and insulin resistance. The work is supported by The University of Tennessee faculty start‐up fund and WHNRC USDA/ARS program funds.