Anti-obesity effect of insulin-like growth factor 1 in naturally aging mice

doi:10.12307/2025.324

Abstract

Abstract: BACKGROUND: In our previous experiments, it was found that transplantation of young adipose stem cells into aged mice would have weight loss effect and improve the inflammatory state in aged mice. Therefore, we speculate that insulin-like growth factor 1 may play an important role in aging and obesity.
OBJECTIVE: To explore the anti-obesity effect of insulin-like growth factor 1 in naturally aging mice.
METHODS: (1) Bioinformatics analysis: Sequencing of adipose tissue from obese patients in the GEO database and transcriptomic sequencing of young mouse adipose stem cells and old adipose stem cells were conducted to analyze insulin-like growth factor 1 expression. (2) Animal experiment verification: Six young C57BL/6J mice and twelve aged C57BL/6J mice (20 months old) were selected. Abdominal adipose tissue and serum insulin-like growth factor 1 expression in young and aged mice were examined by ELISA and qRT-PCR. All the 12 aged mice were randomly divided into two groups with 6 mice in each group: the experimental group was given insulin-like growth factor 1 (50 μg/kg) for 4 continuous weeks, while the control group was given the same amount of phosphate buffer saline. The body mass changes of mice were monitored regularly, glucose tolerance was measured at the end of the experiment, and serum inflammatory factors and inflammatory factors in abdominal white adipose tissue of mice were detected by ELISA. Hematoxylin-eosin staining was used to observe pathological changes in the mouse liver, kidney and abdominal white adipose tissue. The mRNA expression levels of inflammatory factors and PI3K-Akt signaling pathway in abdominal white adipose tissue of mice were detected by qRT-PCR.
RESULTS AND CONCLUSION: Obese patients showed lowly expressed insulin-like growth factor 1 in adipose tissue, but the expression of insulin-like growth factor 1 increased after weight loss surgery. Insulin-like growth factor 1 expressed lowly in aged adipose stem cells. Insulin-like growth factor 1 also showed a low expression in adipose tissue and serum of aged mice. Injection of insulin-like growth factor 1 protein could significantly reduce the body mass of aged mice and improve insulin resistance. Pathological sections of the liver of aged mice revealed fat accumulation. After injection of insulin-like growth factor 1 protein, fat accumulation was significantly improved and the size of fat droplets in adipose tissue was significantly reduced. Insulin-like growth factor 1 injection significantly reduced the expression levels of serum tumor necrosis factor α, interleukin 1β, and interleukin 6 in aged mice, and significantly increased the expression of PI3K-AKT signaling pathway in adipose tissue of aged mice. To conclude, exogenous insulin-like growth factor 1 can reduce body mass, reduce fat droplet size in adipose tissue, and improve liver fat accumulation in aged mice, thereby improving their inflammatory status. Exogenous insulin-like growth factor 1 may activate the PI3K-AKT signaling pathway to improve the inflammatory symptoms in aged mice, thereby improving obesity in naturally aging mice.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: insulin-like growth factor 1, aged, obesity, adipose tissue, insulin resistance, inflammation, PI3K-AKT signaling pathway

CLC Number:

Zhu Peng, Li Yingyu, Lu Xiaoqian, Wu Qiong. Anti-obesity effect of insulin-like growth factor 1 in naturally aging mice[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(12): 2536-2543.

Figures/Tables 6

2.1 生信分析类胰岛素生长因子1表达情况 ①通过GEO数据库中样本为人脂肪组织的测序分析，结果如图1A所示，肥胖组中的类胰岛素生长因子1表达显著降低，但在减肥手术后类胰岛素生长因子1的表达回升。②对青年小鼠脂肪干细胞和老年小鼠脂肪干细胞进行了转录组学测序，结果如图1B所示，发现老年脂肪干细胞低表达类胰岛素生长因子1。因此推测类胰岛素生长因子1可能对于衰老和肥胖具有重要作用。 2.2 动物实验验证结果 2.2.1 实验动物数量分析 ①实验选用2月龄小鼠6只，20月龄小鼠6只进行ELISA和qRT-PCR检测；②选用20月龄C57BL/6J小鼠12只，分为2组，实验过程中无小鼠死亡、脱失等情况发生，进入结果分析12只。 2.2.2 小鼠类胰岛素生长因子1表达为了验证上述生信分析结果，采用qRT-PCR和ELISA检测了青年和老年小鼠腹部脂肪组织和血清类胰岛素生长因子1的表达情况。①qRT-PCR检测小鼠腹部脂肪组织，结果如图2A所示，发现老年小鼠低表达类胰岛素生长因子1 mRNA。②ELISA检测小鼠腹部脂肪组织，结果如图2B所示，同样发现老年小鼠低表达类胰岛素生长因子1。③ELISA检测小鼠血清，结果如图2C所示，依然发现老年小鼠低表达类胰岛素生长因子1。这个结果与上述生信分析结果一致，据此推测类胰岛素生长因子1可能对治疗老年小鼠的肥胖体征具有一定的作用。 2.2.3 小鼠体质量与摄食量为了探究类胰岛素生长因子1对于老年小鼠的具体作用，分别对老年、青年小鼠注射类胰岛素生长因子1蛋白或同等剂量的PBS，定期监测小鼠体质量变化及摄食量。①小鼠体质量变化如图3A所示，从第2周开始，实验组小鼠的体质量与对照组相比有显著性的变化(P < 0.05)，实验结束时，实验组小鼠平均减少体质量7 g，结果表明注射类胰岛素生长因子1蛋白能显著降低老年小鼠体质量。②小鼠摄食量情况如图3B所示，结果表明注射类胰岛素生长因子1蛋白对小鼠摄食量无影响。③连续注射4周类胰岛素生长因子1蛋白后，小鼠的葡萄糖耐受结果如图3C所示，曲线面积如图3D所示，结果发现注射类胰岛素生长因子1有效降低了小鼠的初始血糖，且曲线面积与对照组相比显著降低，说明类胰岛素生长因子1能够改善老年小鼠的胰岛素抵抗。 2.2.4 小鼠肝、肾和脂肪组织病理学观察 ①对照组和实验组小鼠的肝脏病理学切片如图4A所示，在对照组中发现老年小鼠肝脏具有脂肪堆积的情况，注射类胰岛素生长因子1蛋白后，显著改善了这种脂肪堆积。②对照组与实验组肾脏病理学切片如图4B所示，通过观察发现，对照组小鼠肾脏病理学切片与实验组小鼠肾脏病理学切片相比无明显差异。③对照组小鼠与实验组小鼠腹部脂肪组织病理学切片如图4C所示，通过Image J软件对脂滴大小面积进行测量，测量结果如图4D所示，发现实验组小鼠脂滴大小显著减小，说明类胰岛素生长因子1可能是通过减小脂肪组织脂滴大小来减轻体质量的。 2.2.5 小鼠炎症因子检测结果 ①小鼠腹部脂肪组织qRT-PCR检测结果如图5A所示，发现类胰岛素生长因子1能显著降低脂肪组织炎症因子肿瘤坏死因子α、白细胞介素1β、白细胞介素6 mRNA的表达水平。②小鼠血清炎症因子的检测结果如图5B所示，发现类胰岛素生长因子1能显著降低小鼠体内炎症因子肿瘤坏死因子α、白细胞介素1β、白细胞介素6的表达水平，显著增加白细胞介素10的表达水平。③小鼠腹部脂肪组织ELISA检测结果如图5C所示，发现类胰岛素生长因子1能显著降低脂肪组织肿瘤坏死因子α、白细胞介素β的表达水平。这些结果表明，类胰岛素生长因子1能改善老年小鼠体内炎症状况，但具体机制需进一步探究。 2.2.6 小鼠脂肪组织PI3K-AKT信号通路表达情况为了探究类胰岛素生长因子1的作用机制，采用qRT-PCR检测了小鼠腹部脂肪组织PI3K-AKT信号通路mRNA的表达，如图6所示。结果表明，与对照组相比，类胰岛素生长因子1显著提升了腹部脂肪组织PI3K-AKT信号通路的表达，提示类胰岛素生长因子1可能是通过类胰岛素生长因子1信号通路对老年小鼠发挥相关作用的。"

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