Potential Role of Toll‐like Receptor 4 in Obesity‐Induced Adipose Tissue Remodeling

Abstract

Obesity is a state of chronic inflammation which contributes to insulin resistance. Toll‐like receptor (TLR) 4 is involved in adipose tissue (AT) inflammation, but its role in the regulation of extracellular matrix (ECM) genes in AT is unknown. We conducted a study on the effect of high fat diet (HFD) and acute TLR4 activation with lipopolysaccharide (LPS) on ECM gene expression. We also investigated the impact of chronic TLR4 activation by HFD on ECM genes in a wild type (WT) C3H/HeOuJ and TLR4 deficient (KO) C3H/HeJ mice. In the subcutaneous (SC) AT, apart from induction of inflammatory cytokines, there was no effect of LPS challenge on the expression of ECM genes. However, HFD results in significant induction of COL1A1 and COL6A1 (P < 0.05). In the epididymal depot, LPS challenge results in the upregulation of biglycan but a down regulation of lumican and COL6A1 (P < 0.05). Higher expression of biglycan, lumican and COL1A1 (P < 0.05) was induced by HFD. The WT mice had higher ECM gene expression than the KO. Limited effect of HFD was observed in the WT. Significant induction of ECM genes by HFD was observed in both the epididymal and the SC depot of the KO mice. Although HFD leads to induction of transcripts of ECM genes, our results suggest a limited role for TLR4 activation in HFD‐induced AT remodeling. However, the WT has a higher basal expression of the ECM mRNA. This indicates a non‐dietary connection to ECM gene regulation by TLR4.Grant Funding Source: Purdue University