背景:今天,现代生活方式和睡眠模式中断会导致与瘦素水平改变有关的昼夜节律障碍,随后影响广泛的生理过程,并对社会产生重大的健康负担。然而,目前还没有关于生物钟基因和蛋白质的系统综述,瘦素,以及相关的信号通路。
方法:因此,我们系统地回顾了生物钟蛋白质,瘦素,通过搜索Pubmed,以及它们之间的分子机制,Scopus,ProQuest,WebofSciences,和谷歌学者直到2022年9月。在考虑了纳入和排除标准后,选择了20个动物研究。在每个研究中评估偏倚的风险。
结果:结果阐明了昼夜节律基因与瘦素之间的相互关联关系。生物钟基因通过不同的机制调节瘦素的表达和信号,如CLOCK-BMAL1异二聚体,增加PPARs的表达。PPARs诱导C/EBPα的表达,上调瘦素表达的关键因素。CLOCK-BMAL1还诱导Per1和Rev-erb基因的表达。PER1激活mTORC1,mTORC1增强C/EBPα的表达。此外,REV-ERBs激活瘦素信号通路。此外,瘦素通过触发AMPK和ERK/MAPK信号通路控制生物钟基因的表达,调节PPARs的活性。此外,这些分子机制的作用在不同的生理过程和器官中被阐明。
结论:在选择相关疾病的新治疗靶点时,应考虑生物钟基因与瘦素及其影响因素之间的串扰。尤其是肥胖和代谢障碍。
BACKGROUND: Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect a wide range of physiological processes and have significant health burdens on societies. Nevertheless, there has been no systematic
review of circadian clock genes and proteins, leptin, and related signaling pathways.
METHODS: Accordingly, we systematically reviewed circadian clock proteins, leptin, and molecular mechanisms between them by searching Pubmed, Scopus, ProQuest, Web of Sciences, and Google Scholar until September 2022. After considering the inclusion and exclusion criteria, 20 animal studies were selected. The risk of bias was assessed in each study.
RESULTS: The results clarified the reciprocal interconnected relationship between circadian clock genes and leptin. Circadian clock genes regulate leptin expression and signaling via different mechanisms, such as CLOCK-BMAL1 heterodimers, which increase the expression of PPARs. PPARs induce the expression of C/EBPα, a key factor in upregulating leptin expression. CLOCK-BMAL1 also induces the expression of Per1 and Rev-erb genes. PER1 activates mTORC1 and mTORC1 enhances the expression of C/EBPα. In addition, REV-ERBs activate the leptin signaling pathway. Also, leptin controls the expression of circadian clock genes by triggering the AMPK and ERK/MAPK signaling pathways, which regulate the activity of PPARs. Moreover, the roles of these molecular mechanisms are elucidated in different physiological processes and organs.
CONCLUSIONS: Crosstalk between circadian clock genes and leptin and their affecting elements should be considered in the selection of new therapeutic targets for related disorders, especially obesity and metabolic impairments.