Department of Physical Education, Exercise and Immunometabolism Research Group, Post-Graduation Program in Movement Sciences, Sao Paulo State University (UNESP), São Paulo, Brazil.
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil.
J Cell Physiol. 2019 Apr;234(4):5241-5251. doi: 10.1002/jcp.27333. Epub 2018 Sep 21.
Exercise is a powerful tool for prevention and treatment of many conditions related to the cardiovascular system and also chronic low-grade inflammation. Peroxisome proliferator-activated receptors γ (PPARγ) exerts an import role on the regulation of metabolic profile and subsequent inflammatory response, especially in macrophages.
To investigate the effects of 8-week moderate-exercise training on metabolic and inflammatory parameters in mice with PPARγ deficiency in myeloid cells.
Twelve-week old mice bearing PPARγ deletion exclusively in myeloid cells (PPARγlox/lox Lys Cre , knockout [KO]) and littermate controls (PPARγlox/lox Lys Cre , wild type [WT]) were submitted to 8-week exercise training (treadmill running at moderate intensity, 5 days/week). Animals were evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue and peritoneal macrophage inflammation, and basal and stimulated cytokine secretion.
Exercise protocol did not improve glucose metabolism or adiponectin concentrations in serum of KO mice. Moreover, the absence of PPARγ in macrophages exacerbated the proinflammatory profile in sedentary mice. Peritoneal cultured cells had higher tumor necrosis factor-α (TNF-α) secretion in nonstimulated and lipopolysaccharide (LPS)-stimulated conditions and higher Toll-4 receptor (TLR4) gene expression under LPS stimulus. Trained mice showed reduced TNF-α content in adipose tissue independently of the genotype. M2 polarization ability was impaired in KO peritoneal macrophages after exercise training, while adipose tissue-associated macrophages did not present any effect by PPARγ ablation.
Overall, PPARγ seems necessary to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization, affecting also whole body lipid metabolism and adiponectin profile. Exercise training showed as an efficient mechanism to restore the immune response impaired by PPARγ deletion in macrophages.
运动是预防和治疗许多与心血管系统相关的疾病以及慢性低度炎症的有力工具。过氧化物酶体增殖物激活受体 γ（PPARγ）在调节代谢特征和随后的炎症反应方面发挥着重要作用，尤其是在巨噬细胞中。
研究 8 周中等强度运动训练对髓样细胞中 PPARγ 缺陷小鼠代谢和炎症参数的影响。
12 周龄的骨髓细胞中 PPARγ 缺失（PPARγlox/lox Lys Cre+/-，敲除[KO]）和同窝对照（PPARγlox/lox Lys Cre+/-，野生型[WT]）的小鼠接受 8 周的运动训练（在中等强度的跑步机上运行，每周 5 天）。评估动物的食物摄入量、葡萄糖稳态、血清代谢物、脂肪组织和腹膜巨噬细胞炎症以及基础和刺激细胞因子分泌。
运动方案并未改善 KO 小鼠的葡萄糖代谢或血清脂联素浓度。此外，巨噬细胞中 PPARγ 的缺失加剧了久坐不动小鼠的促炎表型。腹膜培养细胞在未刺激和脂多糖（LPS）刺激条件下具有更高的肿瘤坏死因子-α（TNF-α）分泌，在 LPS 刺激下具有更高的 Toll-4 受体（TLR4）基因表达。训练小鼠的脂肪组织中 TNF-α含量降低，与基因型无关。运动训练后，KO 腹膜巨噬细胞的 M2 极化能力受损，而脂肪组织相关巨噬细胞则不受 PPARγ 缺失的影响。
总的来说，PPARγ 似乎对于维持巨噬细胞对炎症刺激的适当反应和巨噬细胞极化是必要的，这也会影响全身脂质代谢和脂联素谱。运动训练是一种有效的机制，可以恢复巨噬细胞中 PPARγ 缺失引起的免疫反应受损。
