近日，以色列魏茨曼科学研究所Ido Amit研究组发布了最新研究进展，他们提出了脂质相关巨噬细胞以Trem2基因依赖的方式调控代谢内环境稳态。该项研究成果发表在2019年7月25日出版的《细胞》杂志上。

利用指数法和转录水平单细胞分选法，该课题组研究人员综合绘制了小鼠和人类在肥胖发生期间的所有脂肪组织免疫细胞分群，由此发现了一个新的和保守存在的Trem2阳性的脂质相关巨噬细胞亚群，并鉴别了与这群细胞相关的标记物、空间定位、起源和功能性通路。小鼠Trem2基因切除的小鼠表现为巨噬细胞下游分子程序性抑制，导致脂肪细胞肥大以及系统性高胆固醇血症、体脂积累和葡萄糖不耐受。这些发现表明Trem2基因信号通路是巨噬细胞对组织水平脂质稳态失衡做出反应的主要途径，并强调Trem2是多种组织病理性代谢途径的关键分子，有望成为代谢性疾病的潜在治疗靶点。

研究人员表示，过去的研究已经阐明了白色脂肪组织中的免疫细胞是参与代谢性疾病发病机制的重要因素，但在肥胖发生过程中驱动脂肪组织免疫细胞重构的分子调控因子仍不清楚。
 

附：英文原文


Title: Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner

Author: Diego Adhemar Jaitin, Lorenz Adlung, Christoph A. Thaiss, Hagit Shapiro, Eran Elinav, Ido Amit

Issue&Volume: Volume 178 Issue 3

Abstract: Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2 + lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

DOI: DOI:https://doi.org/10.1016/j.cell.2019.05.054

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30625-7#