The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice.
The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice.
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DOI：
10.3390/ijms24076828
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发表时间：
2023-04-06
影响因子：
5.6
通讯作者：
Maher, Pamela
中科院分区：
文献类型：
--
作者：
Zahid, Saadia;Dafre, Alcir L. L.;Currais, Antonio;Yu, Jingting;Schubert, David;Maher, Pamela
缺乏瘦素受体并表现出食欲过盛的db/db小鼠表现出能量代谢紊乱，并且是肥胖症和2型糖尿病的模型。老年神经保护剂候选药物CMS 121已被证明在阿尔茨海默病和衰老的动物模型中通过调节代谢是有效的。因此，假设CMS 121可以保护db/db小鼠免受代谢缺陷，从而减少肝脏炎症和肾脏损伤。小鼠在其饮食中用CMS 121处理6个月。与对照db/db小鼠相比，未观察到摄食量和耗氧量、体重或自发活动的变化，但观察到体重降低5%。还观察到葡萄糖耐量改善和HbA 1c和胰岛素水平降低。血液和肝脏甘油三酯和游离脂肪酸降低。尿液中脂肪酸代谢物水平较低，支持代谢改善。肝脏炎症的标志物，包括NF-κB、IL-18、半胱天冬酶3和C反应蛋白，通过CMS 121治疗降低。肾脏损伤的尿液标志物得到改善，如NGAL、丛生蛋白和白蛋白的尿液水平降低所证明。尿液代谢组学研究为肾脏保护提供了进一步的证据。db/db小鼠的线粒体蛋白标志物升高，但CMS 121恢复了NDUFB 8、UQCRC 2和VDAC的肾脏水平。总体而言，长期CMS 121治疗缓解了代谢失衡，肝脏炎症，并减少了肾损伤的标志物。因此，本研究为CMS 121在治疗代谢性疾病中的潜在治疗用途提供了有希望的证据。
db/db mice, which lack leptin receptors and exhibit hyperphagia, show disturbances in energy metabolism and are a model of obesity and type 2 diabetes. The geroneuroprotector drug candidate CMS121 has been shown to be effective in animal models of Alzheimer’s disease and aging through the modulation of metabolism. Thus, the hypothesis was that CMS121 could protect db/db mice from metabolic defects and thereby reduce liver inflammation and kidney damage. The mice were treated with CMS121 in their diet for 6 months. No changes were observed in food and oxygen consumption, body mass, or locomotor activity compared to control db/db mice, but a 5% reduction in body weight was noted. Improved glucose tolerance and reduced HbA1c and insulin levels were also seen. Blood and liver triglycerides and free fatty acids decreased. Improved metabolism was supported by lower levels of fatty acid metabolites in the urine. Markers of liver inflammation, including NF-κB, IL-18, caspase 3, and C reactive protein, were lowered by the CMS121 treatment. Urine markers of kidney damage were improved, as evidenced by lower urinary levels of NGAL, clusterin, and albumin. Urine metabolomics studies provided further evidence for kidney protection. Mitochondrial protein markers were elevated in db/db mice, but CMS121 restored the renal levels of NDUFB8, UQCRC2, and VDAC. Overall, long-term CMS121 treatment alleviated metabolic imbalances, liver inflammation, and reduced markers of kidney damage. Thus, this study provides promising evidence for the potential therapeutic use of CMS121 in treating metabolic disorders.
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DOI：
10.18632/aging.100838
发表时间：
2015-11
期刊：
Aging
影响因子：
--
作者：
Currais A;Goldberg J;Farrokhi C;Chang M;Prior M;Dargusch R;Daugherty D;Armando A;Quehenberger O;Maher P;Schubert D
通讯作者：
Schubert D
DOI：
10.1152/ajprenal.00427.2020
发表时间：
2020-11-01
影响因子：
4.2
作者：
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通讯作者：
Schnellmann, Rick G.
影响因子：
168.9
作者：
Turner, RC;Holman, RR;Ward, JD
通讯作者：
Ward, JD
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
3.3
作者：
Chen, Qian;Ren, Dongwen;Wang, Tao
通讯作者：
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