LNC TINCR Induced by NOD1 Mediates Inflammatory Response in 3T3-L1 Adipocytes

Gene. 2019 May 25;698:150-156. doi: 10.1016/j.gene.2019.02.047. Epub 2019 Mar 6.

Abstract

Objective: Investigating the expression of the lnc RNAs screened above between normal and insulin resistant 3T3-L1 adipocytes. Addressing the mechanism underlying the regulation of inflammation response by lnc TINCR.

Methods: 3T3-L1 preadipocytes were induced to differentiate into mature adipocytes. Oil red O staining was used to find the fat droplets in mature adipocytes. Mature adipocytes were randomized to normal control group and Tri-DAP (NOD1 ligand) group. After the establishment of insulin resistance model, we used deep RNA sequencing(RNA-Seq) to identify lncRNAs that are regulated during NODI activation in mouse adipocytes. Real-time PCR was used to analyze the expression of lnc TINCR, proinflammatory IL-6, TNF-α, Cxcl1 and RIPK2 in the presence or absence of Tri-DAP(10 μg/ml). We employed siRNA against lnc TINCR to confirm its effects in inflammatory response.

Results: Deep RNA sequencing identified 81 lncRNAs and 167 coding genes that were significantly up-related while 78 lncRNAs and 82 coding genes that were significantly down-related greater than twofold during NOD1 activation in adipocytes. We discovered that lnc TINCR, termed lnc TINCR(Tri-DAP-inducible non-protein coding RNA) is greatly upregulated in Tri-DAP activated adipocytes. Moreover knockdown of lnc TINCR dampens the proinflammatory response (P < 0.05; in adipocytes).

Conclusions: lnc TINCR is a positive regulator of inflammation-induced insulin resistance presumably via activation of NOD1 signaling pathways.

Keywords: Inflammation; Insulin resistance; NOD1; lnc RNAs.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Animals
  • Cell Differentiation
  • Inflammation / genetics*
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Mice
  • Nod1 Signaling Adaptor Protein / genetics*
  • Nod1 Signaling Adaptor Protein / metabolism
  • Phosphorylation
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger
  • Sequence Analysis, RNA / methods
  • Signal Transduction

Substances

  • Insulin
  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse
  • RNA, Long Noncoding
  • RNA, Messenger
  • TINCR lncRNA, human