Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Basic Nursing, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Int J Obes (Lond). 2022 Jan;46(1):68-76. doi: 10.1038/s41366-021-00961-9. Epub 2021 Sep 7.
BACKGROUND/OBJECTIVES: Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size.
MATERIALS/SUBJECTS AND METHODS: Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it.
PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-BM exhibited similar adiposity gain as WT chimeras. PAFR mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes.
Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.
背景/目的：血小板激活因子受体（PAFR）的激活控制动物模型中的脂肪组织（AT）扩张。我们的目的有两个：（i）检查 PAFR 信号是否参与人类肥胖，以及（ii）研究 PAF 途径在造血或非造血细胞中控制脂肪细胞大小的作用。
材料/受试者和方法：评估肥胖受试者的临床参数和脂肪组织基因表达。从野生型（WT）或 PAFR 小鼠进行骨髓（BM）移植，以获得主要在造血或非造血细胞衍生细胞中缺乏 PAFR 的嵌合 PAFR 缺陷型小鼠。使用高碳水化合物饮食（HC）诱导 AT 重塑，并评估 PAFR 信号在哪个细胞区室中调节它。此外，用 PAF 处理 3T3-L1 细胞以评估脂肪积累和与之相关的基因表达。
肥胖症患者网膜 AT 中的 PAFR 表达与不同肥胖参数呈负相关，并且在基质血管部分比脂肪细胞中表达更多。与 WT 相比，总 PAFR 增加了肥胖症，而与饮食诱导的肥胖无关。不同的是，接受 PAFR-BM 的 WT 小鼠表现出与 WT 嵌合体相似的肥胖增益。接受 WT-BM 的 PAFR 小鼠表现出与总 PAFR 小鼠相当的肥胖增加，表明 PAFR 信号通过非造血细胞调节脂肪组织扩张。事实上，PAF 处理 3T3-L1 脂肪细胞减少了脂肪积累和脂肪生成基因的表达。
因此，降低的 PAFR 信号可能有利于人类和动物模型中的 AT 积累。重要的是，PAFR 信号，主要在非造血细胞中，特别是在脂肪细胞中，似乎在调节饮食诱导的 AT 扩张中发挥重要作用。
