Obesity is associated with the development of 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 effects. 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 human and mouse models. In 300 individuals with obesity, AT APOM mRNA level was negatively associated with 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. Apom deficiency was associated with a higher inflammatory signature in AT compared with WT mice but not in the 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 the protective role of adipocyte APOM against obesity-induced AT inflammation.
Keywords: adipocytes; adipokines; cytokines; inflammation; lipocalin; lipoproteins; macrophages; obesity; sphingosine-1-phosphate.
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