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基于机器学习和孟德尔随机化分析的肥胖进展中的昼夜节律基因特征

Circadian gene signatures in the progression of obesity based on machine learning and Mendelian randomization analysis.

作者信息

Cheng Zhi'ang, Liu Binghong, Liu Xiaoyong

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

College of Horticulture, South China Agricultural University, Guangzhou, China.

出版信息

Front Nutr. 2024 Sep 16;11:1407265. doi: 10.3389/fnut.2024.1407265. eCollection 2024.

DOI:10.3389/fnut.2024.1407265
PMID:39351493
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11439728/
Abstract

OBJECTIVE

Obesity, a global health concern, is associated with a spectrum of chronic diseases and cancers. Our research sheds light on the regulatory role of circadian genes in obesity progression, providing insight into the immune landscape of obese patients, and introducing new avenues for therapeutic interventions.

METHODS

Expression files of multiple datasets were retrieved from the GEO database. By 80 machine-learning algorithm combinations and Mendelian randomization analysis, we discovered the key circadian genes contributing to and protecting against obesity. Subsequently, an immune infiltration analysis was conducted to examine the alterations in immune cell types and their abundance in the body and to investigate the relationships between circadian genes and immune cells. Furthermore, we delved into the molecular mechanisms of key genes implicated in obesity.

RESULTS

Our study identified three key circadian genes (BHLHE40, PPP1CB, and CSNK1E) associated with obesity. BHLHE40 was found to promote obesity through various pathways, while PPP1CB and CSNK1E counteracted lipid metabolism disorders, and modulated cytokines, immune receptors, T cells, and monocytes.

CONCLUSION

In conclusion, the key circadian genes (BHLHE40, CSNK1E, and PPP1CB) may serve as novel biomarkers for understanding obesity pathogenesis and have significant correlations with infiltrating immune cells, thus providing potential new targets for obese prevention and treatment.

摘要

目的

肥胖是一个全球性的健康问题，与一系列慢性疾病和癌症相关。我们的研究揭示了昼夜节律基因在肥胖进展中的调节作用，深入了解肥胖患者的免疫格局，并为治疗干预引入新途径。

方法

从GEO数据库中检索多个数据集的表达文件。通过80种机器学习算法组合和孟德尔随机化分析，我们发现了导致肥胖和预防肥胖的关键昼夜节律基因。随后，进行了免疫浸润分析，以检查体内免疫细胞类型及其丰度的变化，并研究昼夜节律基因与免疫细胞之间的关系。此外，我们深入研究了与肥胖相关的关键基因的分子机制。

结果

我们的研究确定了三个与肥胖相关的关键昼夜节律基因（BHLHE40、PPP1CB和CSNK1E）。发现BHLHE40通过多种途径促进肥胖，而PPP1CB和CSNK1E则抵消脂质代谢紊乱，并调节细胞因子、免疫受体、T细胞和单核细胞。

结论

总之，关键昼夜节律基因（BHLHE40、CSNK1E和PPP1CB）可能作为理解肥胖发病机制的新型生物标志物，与浸润免疫细胞有显著相关性，从而为肥胖预防和治疗提供潜在的新靶点。

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