Fu Qingan, Liu Jierui, Liu Zhekang, Shen Tianzhou, Yu Qingyun, Zhu Huangxin, Wu Shisheng, Liu Rixiang, Zhang Deju, Liu Xiao, Yin Xiaoping, Liu Jianping, Wu Yanze, Zhang Jing, Yu Peng
Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College Nanchang University Nanchang China.
Cardiovascular Medicine Department The Second Affiliated Hospital of Nanchang University Nanchang China.
Food Sci Nutr. 2025 Jun 23;13(6):e70446. doi: 10.1002/fsn3.70446. eCollection 2025 Jun.
Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition closely associated with obesity and metabolic syndrome, with its global incidence on the rise. This study aims to explore the causal relationship between dietary preferences and NAFLD risk using multi-omics analysis, and to comprehensively explore possible mediating factors and their underlying mechanisms. We analyzed data from genome-wide association studies (GWAS) to assess the potential genetic links between various dietary preferences and NAFLD. A two-step Mendelian randomization (MR) analysis was conducted to evaluate whether dietary preferences affect NAFLD risk by regulating inflammatory factors. Further, co-localization analysis was used to identify gene loci driving the causal relationships between dietary preferences and NAFLD risk. Finally, clinical cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) and bioinformatics analysis were used to validate the findings.MR analysis revealed that a preference for a low-calorie diet significantly reduces NAFLD risk by modulating DNER. Co-localization analysis identified the FTO gene variant rs28429148 as a key driver of the causal relationship between soft cheese and fruit juice preferences, with soft cheese increasing and fruit juice reducing NAFLD risk. These findings were further validated by clinical cross-sectional and bioinformatics analysis. This study, for the first time, comprehensively elucidates the causal relationship between dietary preferences and NAFLD risk from a multi-omics perspective and identifies FTO and DNER as potential therapeutic targets. These findings provide new insights into the importance of personalized dietary interventions in the prevention of NAFLD and informs clinical treatment.
非酒精性脂肪性肝病（NAFLD）是一种与肥胖和代谢综合征密切相关的常见疾病，其全球发病率呈上升趋势。本研究旨在通过多组学分析探讨饮食偏好与NAFLD风险之间的因果关系，并全面探究可能的中介因素及其潜在机制。我们分析了全基因组关联研究（GWAS）的数据，以评估各种饮食偏好与NAFLD之间的潜在遗传联系。进行了两步孟德尔随机化（MR）分析，以评估饮食偏好是否通过调节炎症因子影响NAFLD风险。此外，共定位分析用于确定驱动饮食偏好与NAFLD风险之间因果关系的基因位点。最后，利用美国国家健康与营养检查调查（NHANES）的临床横断面数据和生物信息学分析对研究结果进行验证。MR分析显示，对低热量饮食的偏好通过调节DNER显著降低NAFLD风险。共定位分析确定FTO基因变体rs28429148是软奶酪和果汁偏好与NAFLD风险之间因果关系的关键驱动因素，软奶酪增加NAFLD风险，而果汁降低NAFLD风险。这些发现通过临床横断面和生物信息学分析得到进一步验证。本研究首次从多组学角度全面阐明了饮食偏好与NAFLD风险之间的因果关系，并确定FTO和DNER为潜在治疗靶点。这些发现为个性化饮食干预在预防NAFLD中的重要性提供了新见解，并为临床治疗提供了参考。
