Yuan Fang, Zhang Qianqian, Dong Haiyan, Xiang Xinxin, Zhang Weizhen, Zhang Yi, Li Yin
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing100191, China.
Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing100191, China.
J Transl Int Med. 2021 Jul 2;9(2):84-97. doi: 10.2478/jtim-2021-0025. eCollection 2021 Jun.
Obesity is the accumulation of adipose tissue caused by excess energy in the body, accompanied by long-term chronic low-grade inflammation of adipose tissue. More than 50% of interstitial cells in adipose tissue are macrophages, which produce cytokines closely related to insulin resistance. Macrophage biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2 (anti-inflammatory). This study aimed to investigate the effect of gastric hormone des-acyl ghrelin (DAG) on the polarization phenotype of macrophages and elucidate the role of macrophages in adipose tissue inflammation and insulin sensitivity and its molecular mechanism.
Mice were subcutaneously administrated with DAG in osmotic minipumps. The mice were fed a normal diet or a high-fat diet (HFD). Different macrophage markers were detected by real-time revere transcription polymerase chain reaction.
Exogenous administration of DAG significantly inhibited the increase of adipocyte volume caused by HFD and reduced the number of rosette-like structures in adipose tissue. HFD in the control group significantly increased M1 macrophage markers, tumor necrosis factor α (TNFα), and inducible NO synthase (iNOS). However, these increases were reduced or even reversed after DAG administration . The M2 markers, macrophage galactose type C-type Lectin-1 (MGL1), arginase 1 (Arg1), and macrophage mannose receptor 1 (MRC1) were decreased by HFD, and the downward trend was inhibited or reversed after DAG administration. Although Arg1 was elevated after HFD, the fold increase after DAG administration was much greater than that in the control group.
DAG inhibits adipose tissue inflammation caused by HFD, reduces infiltration of macrophages in adipose tissue, and promotes polarization of macrophages to M2, thus alleviating obesity and improving insulin sensitivity.
肥胖是体内能量过剩导致的脂肪组织堆积，并伴有脂肪组织长期慢性低度炎症。脂肪组织中超过50%的间质细胞是巨噬细胞，其产生与胰岛素抵抗密切相关的细胞因子。巨噬细胞生物学受两种极化表型驱动，即M1（促炎）和M2（抗炎）。本研究旨在探讨胃激素去酰基胃饥饿素（DAG）对巨噬细胞极化表型的影响，并阐明巨噬细胞在脂肪组织炎症和胰岛素敏感性中的作用及其分子机制。
通过渗透微型泵给小鼠皮下注射DAG。小鼠喂食正常饮食或高脂饮食（HFD）。通过实时逆转录聚合酶链反应检测不同的巨噬细胞标志物。
外源性给予DAG可显著抑制高脂饮食引起的脂肪细胞体积增加，并减少脂肪组织中玫瑰花样结构的数量。对照组的高脂饮食显著增加了M1巨噬细胞标志物、肿瘤坏死因子α（TNFα）和诱导型一氧化氮合酶（iNOS）。然而，给予DAG后，这些增加被减少甚至逆转。高脂饮食使M2标志物、巨噬细胞半乳糖型C型凝集素-1（MGL1）、精氨酸酶1（Arg1）和巨噬细胞甘露糖受体1（MRC1）减少，给予DAG后下降趋势受到抑制或逆转。尽管高脂饮食后Arg1升高，但给予DAG后的增加倍数远大于对照组。
DAG抑制高脂饮食引起的脂肪组织炎症，减少巨噬细胞在脂肪组织中的浸润，并促进巨噬细胞向M2极化，从而减轻肥胖并改善胰岛素敏感性。
