Association of a variant in the gene encoding for ERV1/ChemR23 with reduced inflammation in visceral adipose tissue from morbidly obese individuals

Sci Rep. 2017 Nov 16;7(1):15724. doi: 10.1038/s41598-017-15951-z.

Abstract

Obesity comorbidities are closely associated with chronic low-grade adipose tissue inflammation. A number of SNPs associated with inflammation has been identified, underscoring the impact of genetic determinants on this process. Here, we screened SNPs in genes with pro-inflammatory (IL-1β, IL-6, STAT3 and JAK2), anti-inflammatory (IL-10 and SOCS3) and pro-resolving (ERV1/ChemR23) properties in 101 obese and 99 non-obese individuals. Among the SNPs analyzed, we identified that individuals carrying a C allele in the rs1878022 polymorphism of the ERV1/ChemR23 gene, which encodes for the receptor of the pro-resolving mediator RvE1, had increased ERV1/ChemR23 protein expression and reduced levels of the inflammatory cytokine IL-6 in adipose tissue. Moreover, patients carrying the C allele in homozygosity had lower plasma levels of IL-6, IFN-α2, IL-15, IL-1ra, IL-10, GM-CSF, G-CSF and VEGF and enhanced leukocyte responsiveness to RvE1. C-carriers also exhibited decreased TAG to HDL ratio, a surrogate marker of insulin resistance and a predictor of incident fatty liver. Finally, we confirmed in vivo that the ERV1/ChemR23 receptor regulates systemic and tissue inflammation since mice lacking ERV1/ChemR23 expression showed increased IL-6 levels in adipose tissue and peritoneal macrophages. Together, our study identified an ERV1/ChemR23 variant that protects patients with obesity from excessive inflammatory burden.

MeSH terms

  • Animals
  • Female
  • Gene Frequency / genetics
  • Genetic Association Studies*
  • Homozygote
  • Humans
  • Inflammation / genetics*
  • Inheritance Patterns / genetics
  • Interleukin-6 / metabolism
  • Intra-Abdominal Fat / pathology*
  • Liver / pathology
  • Male
  • Mice
  • Middle Aged
  • Models, Genetic
  • Obesity, Morbid / genetics*
  • Omentum / pathology
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Chemokine / genetics*

Substances

  • CMKLR1 protein, human
  • Interleukin-6
  • Receptors, Chemokine