The adipocyte apolipoprotein M is negatively associated with inflammation

Abstract

Obesity is associated with the development of a local adipose tissue (AT) and systemic inflammation. Most adipokines are upregulated with obesity and have pro-inflammatory properties. Few are downregulated and possess beneficial anti-inflammatory effect. The apolipoprotein M (APOM) is an adipokine whose expression is low during obesity and associated with a metabolically healthy AT. Here, the role of adipose-derived APOM on obesity-associated AT inflammation was investigated by measuring the expression of pro-inflammatory genes in humans and mice models. In 300 individuals with obesity, AT APOM mRNA level was negatively associated to plasma hs-CRP. The inflammatory profile was assessed in Apom-/- and WT mice fed a normal chow diet (NCD), or a high fat diet (HFD) to induce AT inflammation. After HFD, mice had a higher inflammatory profile in AT and liver, and a 50% lower Apom gene expression compared with NCD-fed mice. The Apom deficiency was associated with a higher inflammatory signature in AT compared with WT mice, but not in liver. Adeno-associated viruses encoding human APOM were used to induce APOM overexpression: in vivo, in WT mice AT prior to HFD; in vitro, in human adipocytes which conditioned media was applied to ThP-1 macrophages. The murine AT overexpressing APOM gene had a reduced inflammatory profile. The macrophages treated with APOM-enriched media from adipocytes exhibited lower IL6 and MCP1 gene expression compared with macrophages treated with control media, independently of S1P. Our study highlights a protective role of adipocyte APOM against obesity-induced AT inflammation.