PDF(Pubmed)
Abstract：
UNASSIGNED: Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease.
UNASSIGNED: Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 μg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin-eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKβ)/AMPK signaling pathway activation.
UNASSIGNED: Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKβ/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice.
UNASSIGNED: Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKβ/AMPK signaling pathway in kidney tissue.
UNASSIGNED: Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 μg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin-eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKβ)/AMPK signaling pathway activation.
UNASSIGNED: Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKβ/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice.
UNASSIGNED: Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKβ/AMPK signaling pathway in kidney tissue.
摘要：
■利拉鲁肽,胰高血糖素样肽-1受体激动剂，已经被证明可以调节血糖和控制体重，但其治疗肥胖相关肾病的能力研究甚少。因此,本研究旨在观察利拉鲁肽抗肥胖相关肾脏疾病的特点和潜在机制。
■将36只C57BL/6J雄性小鼠随机分为6组(每组n=6)。通过连续喂养高脂饮食（HFD）12周，在小鼠中诱发肥胖相关的肾病。12周后,利拉鲁肽（0.6mg/kg）和AMP激活的蛋白激酶（AMPK）激动剂硼替佐米（200μg/kg）注射12周，分别。采用酶联免疫吸附试验检测总胆固醇水平，甘油三酯，低密度脂蛋白胆固醇，血尿素氮,血清肌酐，以及尿液中的尿蛋白。此外,用苏木精-伊红染色和高碘酸-希夫染色观察肾组织的病理变化;免疫组化,westernblot,和实时定量PCR评估钙调蛋白依赖性蛋白激酶激酶β（CaMKKβ）/AMPK信号通路的激活。
■利拉鲁肽显著降低血清脂质负荷，改善肾功能，减轻HFD诱导的肥胖相关肾脏疾病小鼠模型的肾脏组织病理学损伤和糖原沉积。此外,利拉鲁肽还显著抑制HFD诱导小鼠肾组织中CaMKKβ/AMPK信号通路。然而,硼替佐米部分逆转了利拉鲁肽对HDF诱导的小鼠肾病的治疗作用。
■利拉鲁肽对肥胖相关的肾脏疾病有治疗作用，这种作用可以通过抑制肾组织中的CaMKKβ/AMPK信号通路来实现。
■将36只C57BL/6J雄性小鼠随机分为6组(每组n=6)。通过连续喂养高脂饮食（HFD）12周，在小鼠中诱发肥胖相关的肾病。12周后,利拉鲁肽（0.6mg/kg）和AMP激活的蛋白激酶（AMPK）激动剂硼替佐米（200μg/kg）注射12周，分别。采用酶联免疫吸附试验检测总胆固醇水平，甘油三酯，低密度脂蛋白胆固醇，血尿素氮,血清肌酐，以及尿液中的尿蛋白。此外,用苏木精-伊红染色和高碘酸-希夫染色观察肾组织的病理变化;免疫组化,westernblot,和实时定量PCR评估钙调蛋白依赖性蛋白激酶激酶β（CaMKKβ）/AMPK信号通路的激活。
■利拉鲁肽显著降低血清脂质负荷，改善肾功能，减轻HFD诱导的肥胖相关肾脏疾病小鼠模型的肾脏组织病理学损伤和糖原沉积。此外,利拉鲁肽还显著抑制HFD诱导小鼠肾组织中CaMKKβ/AMPK信号通路。然而,硼替佐米部分逆转了利拉鲁肽对HDF诱导的小鼠肾病的治疗作用。
■利拉鲁肽对肥胖相关的肾脏疾病有治疗作用，这种作用可以通过抑制肾组织中的CaMKKβ/AMPK信号通路来实现。
