Lipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo.

Alison Hall,Ingeborg D Welters,Paul Trayhurn,Martin Leuwer

doi:10.7717/peerj.1428

Abstract

Background. Adipose tissue contributes to the inflammatory response through production of cytokines, recruitment of macrophages and modulation of the adiponectin system. Previous studies have identified a down-regulation of adiponectin in pathologies characterised by acute (sepsis and endotoxaemia) and chronic inflammation (obesity and type-II diabetes mellitus). In this study, we investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures.Methods. 25 mg/kg LPS was injected intra-peritoneally into C57BL/6J mice, equivalent volumes of normal saline were used in control animals. Mice were killed at 4 or 24 h post injection and tissues harvested. Murine adipocytes (3T3-L1) and myocytes (C2C12) were grown in standard culture, treated with LPS (0.1 µg/ml–10 µg/ml) and harvested at 4 and 24 h. RNA was extracted and qPCR was conducted according to standard protocols and relative expression was calculated.Results. After LPS treatment there was a significant reduction after 4 h in gene expression of adipo R1 in muscle and peri-renal fat and of adipo R2 in liver, peri-renal fat and abdominal wall subcutaneous fat. After 24 h, significant reductions were limited to muscle. Cell culture extracts showed varied changes with reduction in adiponectin and adipo R2 gene expression only in adipocytes.Conclusions. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS. The trend towards base line after 24 h in tissue depots may reflect counter-regulatory mechanisms. Adiponectin receptor regulation differs in the tissues investigated.

Highlights

White Adipose Tissue (WAT) is known to be a dynamic secretory organ in its own right, secreting a number of compounds called adipokines (Robinson, Prins & Venkatesh, 2011)
Adiponectin receptors are down-regulated in murine endotoxaemia Expression of adiponectin receptors was detected in all murine tissues examined. 4 h after treatment with LPS, there were significant reductions in adipoR1 gene expression in skeletal muscle (9.8 fold reduction, p = 0.017) and peri-renal fat (PRF) (1.6 fold reduction, p = 0.008) (Table 1A and Data S2)
Cell-type specific downregulation of adiponectin receptors To identify whether the effects of LPS in vivo reflect a direct effect of LPS treatment on specific cell types, we examined relevant cell lines, using LPS as a direct stimulus in cell cultures

Summary

Introduction

White Adipose Tissue (WAT) is known to be a dynamic secretory organ in its own right, secreting a number of compounds called adipokines (Robinson, Prins & Venkatesh, 2011) These biologically active proteins act as inflammatory mediators and play a major role in metabolic derangements in chronic inflammatory disorders such as type 2 Diabetes mellitus (DM) and the metabolic syndrome (Kadowaki et al, 2006; Kern et al, 2003). We investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS.

Methods

Results

Discussion

Conclusion