CTRP1 prevents high fat diet-induced obesity and improves glucose homeostasis in obese and STZ-induced diabetic mice.
CTRP1 prevents high fat diet-induced obesity and improves glucose homeostasis in obese and STZ-induced diabetic mice.
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CTRP1 可预防高脂肪饮食诱导的肥胖，并改善肥胖和 STZ 诱导的糖尿病小鼠的葡萄糖稳态。
DOI：
10.1186/s12967-022-03672-5
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发表时间：
2022-10-04
影响因子：
7.4
通讯作者：
Zhang, Chunbo
中科院分区：
文献类型：
--
作者：
Ren, Mingzhi;Pan, Jianfei;Yu, Xueying;Chang, Kaile;Yuan, Xiaopeng;Zhang, Chunbo
C1 q/肿瘤坏死因子相关蛋白1（CTRP 1）是由脂肪组织分泌的脂肪因子，与软骨细胞增殖、炎症和葡萄糖稳态相关。然而，对代谢紊乱的治疗作用及其机制尚不清楚。本研究旨在探讨CTRP 1在肥胖和糖尿病治疗中的作用和机制。通过流体动力学注射将含有人CTRP 1的质粒递送到小鼠体内，其维持CTRP 1在肝脏中的表达和血液中的高蛋白水平。采用高脂饮食（HFD）喂养的小鼠和STZ诱导的糖尿病模型，研究CTRP 1对肥胖、葡萄糖稳态、胰岛素抵抗和肝脏脂质积聚的影响。分别采用H&E染色法、油红O染色法、葡萄糖耐量试验、胰岛素耐量试验、代谢笼法检测肝脏和脂肪组织脂质蓄积、葡萄糖耐量、胰岛素敏感性、摄食量和能量消耗。使用qPCR和蛋白质印迹法确定代谢相关基因和信号通路。在高血液循环的情况下，CTRP 1可以预防HFD喂养小鼠的肥胖、高血糖、胰岛素抵抗和脂肪肝。CTRP 1还改善了肥胖和STZ诱导的糖尿病小鼠的葡萄糖代谢和胰岛素抵抗。代谢笼研究表明，CTRP 1减少了食物摄入量，增加了能量消耗。机制研究表明，CTRP 1上调血液中的瘦素蛋白水平，棕色脂肪组织中的产热基因表达，以及负责白色脂肪组织（WAT）中的脂解和糖酵解的基因表达。CTRP 1还下调WAT中炎症基因的表达。CTRP 1过表达可激活AMPK和PI 3 K/Akt信号通路，抑制ERK信号通路。这些结果表明，CTRP 1可以通过上调能量消耗和减少食物摄入来改善葡萄糖稳态，并预防HFD诱导的肥胖和脂肪肝，表明CTRP 1可以作为治疗代谢性疾病的有希望的靶点。在线版本包含补充材料，可通过10.1186/s12967-022-03672-5获得。
C1q/tumor necrosis factor-related protein 1 (CTRP1) is an adipokine secreted by adipose tissue, related to chondrocyte proliferation, inflammation, and glucose homeostasis. However, the therapeutic effects on metabolic disorders and the underlying mechanism were unclear. Here, we investigated the functions and mechanisms of CTRP1 in treating obesity and diabetes. The plasmid containing human CTRP1 was delivered to mice by hydrodynamic injection, which sustained expression of CTRP1 in the liver and high protein level in the blood. High-fat diet (HFD) fed mice and STZ-induced diabetes model were used to study the effects of CTRP1 on obesity, glucose homeostasis, insulin resistance, and hepatic lipid accumulation. The lipid accumulation in liver and adipose tissue, glucose tolerance, insulin sensitivity, food intake, and energy expenditure were detected by H&E staining, Oil-Red O staining, glucose tolerance test, insulin tolerance test, and metabolic cage, respectively. The metabolic-related genes and signal pathways were determined using qPCR and western blotting. With high blood circulation, CTRP1 prevented obesity, hyperglycemia, insulin resistance, and fatty liver in HFD-fed mice. CTRP1 also improved glucose metabolism and insulin resistance in obese and STZ-induced diabetic mice. The metabolic cage study revealed that CTRP1 reduced food intake and enhanced energy expenditure. The mechanistic study demonstrated that CTRP1 upregulated the protein level of leptin in blood, thermogenic gene expression in brown adipose tissue, and the gene expression responsible for lipolysis and glycolysis in white adipose tissue (WAT). CTRP1 also downregulated the expression of inflammatory genes in WAT. Overexpression of CTRP1 activated AMPK and PI3K/Akt signaling pathways and inhibited ERK signaling pathway. These results demonstrate that CTRP1 could improve glucose homeostasis and prevent HFD-induced obesity and fatty liver through upregulating the energy expenditure and reducing food intake, suggesting CTRP1 may serve as a promising target for treating metabolic diseases. The online version contains supplementary material available at 10.1186/s12967-022-03672-5.
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DOI：
10.1073/pnas.0403760101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Wong, GW;Wang, J;Lodish, HF
通讯作者：
Lodish, HF
C1qTNF 相关蛋白 1 通过激活 AKT 减轻阿霉素诱导的心脏损伤
影响因子：
6.1
作者：
Chen, Hongrui;Gao, Lu;Liu, Yuzhou
通讯作者：
Liu, Yuzhou
影响因子：
4.6
作者：
Barbieri, Diego;Goicoechea, Marian;Luno, Jose
通讯作者：
Luno, Jose
影响因子：
29
作者：
Kubota, Naoto;Yano, Wataru;Kadowaki, Takashi
通讯作者：
Kadowaki, Takashi
影响因子：
37.8
作者：
Hill JO;Wyatt HR;Peters JC
通讯作者：
Peters JC