Impact of tissue macrophage proliferation on peripheral and systemic insulin resistance in obese mice with diabetes.
Impact of tissue macrophage proliferation on peripheral and systemic insulin resistance in obese mice with diabetes.
复制标题
DOI：
10.1136/bmjdrc-2020-001578
复制
发表时间：
2020-10
影响因子：
4.1
通讯作者：
Araki E
中科院分区：
文献类型：
--
作者：
Morita Y;Senokuchi T;Yamada S;Wada T;Furusho T;Matsumura T;Ishii N;Nishida S;Nishida S;Motoshima H;Komohara Y;Yamagata K;Araki E
肥胖相关的胰岛素抵抗是2型糖尿病广泛接受的病理生理特征。全身代谢和免疫密切相关，肥胖代表免疫功能受损，使个体易患全身性慢性炎症。肥胖患者外周胰岛素靶组织中巨噬细胞浸润和活化增加与胰岛素抵抗密切相关。使用巨噬细胞特异性增殖抑制小鼠模型（mac-p27 Tg），我们以前报道，抑制斑块炎症减少动脉粥样硬化和改善斑块稳定。然而，没有提供增殖的巨噬细胞负责诱导胰岛素抵抗的直接证据。mac-p27 Tg小鼠喂饲高脂饲料，并研究葡萄糖代谢、组织学变化、巨噬细胞极化和组织功能，以揭示组织巨噬细胞增殖在胰岛素抵抗和肥胖中的意义。mac-p27 Tg小鼠显示出改善的葡萄糖耐量和胰岛素敏感性，沿着炎性巨噬细胞的数量和比率的降低。肥胖诱导的炎症和氧化应激在白色脂肪组织、肝脏和腓肠肌中减弱。与胰岛素抵抗相关的组织学变化，如肝脏脂肪变性/纤维化、脂肪细胞增大和骨骼肌纤维向快型转化，在mac-p27 Tg小鼠中得到改善。血清肿瘤坏死因子α和游离脂肪酸降低，可能部分影响胰岛素敏感性改善和组织学变化。脂肪组织、肝脏和骨骼肌中的巨噬细胞增殖参与促进全身性胰岛素抵抗的发展。通过抑制巨噬细胞增殖来控制组织巨噬细胞的数量可能是胰岛素抵抗和2型糖尿病的治疗靶点。
Obesity-related insulin resistance is a widely accepted pathophysiological feature in type 2 diabetes. Systemic metabolism and immunity are closely related, and obesity represents impaired immune function that predisposes individuals to systemic chronic inflammation. Increased macrophage infiltration and activation in peripheral insulin target tissues in obese subjects are strongly related to insulin resistance. Using a macrophage-specific proliferation inhibition mouse model (mac-p27Tg), we previously reported that suppressed plaque inflammation reduced atherosclerosis and improved plaque stabilization. However, the direct evidence that proliferating macrophages are responsible for inducing insulin resistance was not provided. The mac-p27Tg mice were fed a high-fat diet, and glucose metabolism, histological changes, macrophage polarization, and tissue functions were investigated to reveal the significance of tissue macrophage proliferation in insulin resistance and obesity. The mac-p27Tg mice showed improved glucose tolerance and insulin sensitivity, along with a decrease in the number and ratio of inflammatory macrophages. Obesity-induced inflammation and oxidative stress was attenuated in white adipose tissue, liver, and gastrocnemius. Histological changes related to insulin resistance, such as liver steatosis/fibrosis, adipocyte enlargement, and skeletal muscle fiber transformation to fast type, were ameliorated in mac-p27Tg mice. Serum tumor necrosis factor alpha and free fatty acid were decreased, which might partially impact improved insulin sensitivity and histological changes. Macrophage proliferation in adipose tissue, liver, and skeletal muscle was involved in promoting the development of systemic insulin resistance. Controlling the number of tissue macrophages by inhibiting macrophage proliferation could be a therapeutic target for insulin resistance and type 2 diabetes.
登录
查看更多内容
巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
DOI：
10.1073/pnas.87.12.4600
发表时间：
1990-06-01
影响因子：
11.1
作者：
GORDON, D;REIDY, MA;SCHWARTZ, SM
通讯作者：
SCHWARTZ, SM
影响因子：
1.7
作者：
Della Vedova MC;Muñoz MD;Santillan LD;Plateo-Pignatari MG;Germanó MJ;Rinaldi Tosi ME;Garcia S;Gomez NN;Fornes MW;Gomez Mejiba SE;Ramirez DC
通讯作者：
Ramirez DC
影响因子：
--
作者：
MRAD, JA;YAKUBU, F;HILL, JO
通讯作者：
HILL, JO
影响因子：
2.5
作者：
Denies, Maxwell S;Johnson, Jordan;Maliphol, Amanda B;Bruno, Michael;Kim, Annabelle;Rizvi, Abbas;Rustici, Kevyn;Medler, Scott
通讯作者：
Medler, Scott