Institute of Metabolic and Cardiovascular Diseases (I2MC), Team MetaDiab, Institut National de la Santé et de la Recherche Médicale (Inserm), Université Toulouse III, Paul Sabatier (UPS), UMR1297, Toulouse, France.
Nantes Université, CNRS, INSERM, Institut du Thorax, Nantes, France; Nantes Université, CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, Nantes, France; Mass Spectrometry Core Facility, CRNH-Ouest, Nantes, France.
J Lipid Res. 2024 Oct;65(10):100648. doi: 10.1016/j.jlr.2024.100648. Epub 2024 Sep 19.
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.
肥胖与局部脂肪组织（AT）和全身炎症的发展有关。大多数脂肪因子在肥胖时上调，并具有促炎特性。很少有下调，并具有有益的抗炎作用。载脂蛋白 M（APOM）是一种脂肪因子，其在肥胖期间表达水平较低，与代谢健康的 AT 相关。在这里，通过测量人源和鼠源模型中促炎基因的表达，研究了脂肪源性 APOM 在肥胖相关 AT 炎症中的作用。在 300 名肥胖个体中，AT APOM mRNA 水平与血浆 hs-CRP 呈负相关。在 Apom 和 WT 小鼠中评估了炎症特征，这些小鼠分别用正常饮食（NCD）或高脂肪饮食（HFD）喂养以诱导 AT 炎症。在用 HFD 喂养后，与用 NCD 喂养的小鼠相比，小鼠的 AT 和肝脏中的炎症特征更高，并且 Apom 基因表达降低了 50%。与 WT 小鼠相比，Apom 缺乏症与 AT 中的更高炎症特征相关，但与肝脏无关。用编码人 APOM 的腺相关病毒诱导 APOM 过表达：在体内，在 WT 小鼠接受 HFD 之前的 AT 中；在体外，在人脂肪细胞中，用其条件培养基处理 ThP-1 巨噬细胞。过表达 APOM 基因的鼠 AT 具有较低的炎症特征。与用对照培养基处理的巨噬细胞相比，用富含 APOM 的脂肪细胞培养基处理的巨噬细胞的 IL6 和 MCP1 基因表达降低，这与 S1P 无关。我们的研究强调了脂肪细胞 APOM 对肥胖诱导的 AT 炎症的保护作用。
