Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhidong Road, Wuhan, Hubei, 430000, PR China.
Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhidong Road, Wuhan, Hubei, 430000, PR China.
Diabetes Metab Syndr. 2023 Oct;17(10):102854. doi: 10.1016/j.dsx.2023.102854. Epub 2023 Sep 14.
Klotho was first identified as a gene associated with aging and longevity in 1997. α-Klotho is an anti-aging protein and its role in energy metabolism, various cardiovascular diseases (CVDs), and metabolic disorders is increasingly being recognized. In this review, we aimed to outline the potential protective role and therapeutic prospects of α-Klotho in energy metabolism and cardiometabolic diseases (CMDs).
We comprehensively reviewed the relevant literature in PubMed using the keywords 'Klotho', 'metabolism', 'cardiovascular', 'diabetes', 'obesity', 'metabolic syndrome', and 'nonalcoholic fatty liver disease'.
α-Klotho can be divided into membrane-bound Klotho, secreted Klotho, and the most studied circulating soluble Klotho that can act as a hormone. Klotho gene polymorphisms have been implicated in energy metabolism and CMDs. α-Klotho can inhibit insulin/insulin growth factor-1 signaling and its overexpression can lead to a 'healthy insulin resistance' and may exert beneficial effects on the regulation of glycolipid metabolism and central energy homeostasis. α-Klotho, mainly serum Klotho, has been revealed to be protective against CVDs, diabetes and its complications, obesity, and nonalcoholic fatty liver disease. Human recombinant Klotho protein/Klotho gene delivery, multiple drugs, or natural products, and exercise can increase α-Klotho expression.
Overall, α-Klotho has demonstrated its potential as a promising target for modulating energy metabolism and CMDs, and further research is needed to explore its utilization in clinical practice in the future.
Klotho 于 1997 年首次被鉴定为与衰老和长寿相关的基因。α-Klotho 是一种抗衰老蛋白，其在能量代谢、各种心血管疾病 (CVD) 和代谢紊乱中的作用正日益得到认可。在本综述中，我们旨在概述 α-Klotho 在能量代谢和心脏代谢疾病 (CMD) 中的潜在保护作用和治疗前景。
我们使用关键词“Klotho”、“代谢”、“心血管”、“糖尿病”、“肥胖”、“代谢综合征”和“非酒精性脂肪性肝病”，在 PubMed 上全面检索了相关文献。
α-Klotho 可分为膜结合 Klotho、分泌型 Klotho 和研究最多的循环可溶性 Klotho，后者可作为激素发挥作用。Klotho 基因多态性与能量代谢和 CMD 有关。α-Klotho 可抑制胰岛素/胰岛素生长因子-1 信号，其过表达可导致“健康的胰岛素抵抗”，并可能对调节糖脂代谢和中枢能量稳态产生有益影响。α-Klotho（主要是血清 Klotho）已被证明可预防 CVD、糖尿病及其并发症、肥胖和非酒精性脂肪性肝病。人重组 Klotho 蛋白/ Klotho 基因传递、多种药物或天然产物以及运动可以增加 α-Klotho 的表达。
总的来说，α-Klotho 已显示出作为调节能量代谢和 CMD 的有前途的靶点的潜力，未来需要进一步研究以探索其在临床实践中的应用。
