Association of circulating fatty acids with metabolic dysfunction-associated steatotic liver disease: A cross-sectional analysis and Mendelian randomization study

IF 2.9 Q3 NUTRITION & DIETETICS

Clinical nutrition ESPEN Pub Date : 2025-07-16 DOI:10.1016/j.clnesp.2025.07.027

Zhibing Liu , Peng Wang , Yiming Wang , Jing Yu , Qingxuan Wang , Jibin Li , Dan Shi

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引用次数: 0

Abstract

Background & aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with limited therapeutic options. Circulating fatty acids (FAs) have been linked to MASLD, but their specific roles and potential causality remain unclear. This study aimed to clarify the associations between FAs and MASLD.

Methods

This study analyzed data from the National Health and Nutrition Examination Survey 2011–2014, including 3084 participants with serum FAs concentrations (% total FAs). MASLD status was assessed using the Fatty Liver Index (FLI) or the U.S. Fatty Liver Index (USFLI). Odds ratios (OR) and 95 % confidence intervals (CI) of MASLD risk were evaluated using weighted logistic regression. Mendelian randomization (MR) analysis for FAs with MASLD was conducted, and the principal analysis employed the inverse variance weighted approach.

Results

In observational analysis, we identified 1500 cases of MASLD. Saturated FAs (SFAs) were positively associated with MASLD risk [OR_Q3vsQ1: 2.41 (95 % CI: 1.56–3.74)], whereas polyunsaturated FAs (PUFAs) and omega-6 PUFAs showed the negative associations [OR_Q3vsQ1: 0.49 (0.30–0.80) and OR_Q3vsQ1: 0.46 (0.27–0.79), respectively]. Among 30 individual FAs, 7 were associated with an increased risk of MASLD, with the highest risk observed for dihomo-gamma-linolenic acid [OR_Q3vsQ1: 2.07 (1.30–3.28)]. In contrast, 3 FAs showed an inverse association, with the lowest risk observed for linoleic acid [OR_Q3vsQ1: 0.50 (0.28–0.90)]. MR analysis revealed negative causal relationships between genetically predicted omega-6 PUFAs/total fatty acids (TFA) [OR: 0.80 (0.65–0.99)], PUFAs/TFA [OR: 0.73 (0.63–0.84)] and MASLD.

Conclusions

There are differential associations between individual FAs and collective fatty acid classes with MASLD risk, and omega-6 PUFAs may serve as stable biomarkers for potential prevention and treatment of MASLD.

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循环脂肪酸与代谢功能障碍相关的脂肪变性肝病的关联：横断面分析和孟德尔随机化研究

背景与目的：代谢功能障碍相关的脂肪变性肝病（MASLD）是一种普遍的疾病，治疗选择有限。循环脂肪酸（FAs）与MASLD有关，但其具体作用和潜在因果关系尚不清楚。本研究旨在阐明FAs与MASLD之间的关系。方法：本研究分析了2011-2014年全国健康与营养调查数据，包括3084名血清FAs浓度（占总FAs的百分比）的参与者。使用脂肪肝指数（FLI）或美国脂肪肝指数（USFLI）评估MASLD状态。使用加权逻辑回归评估MASLD风险的优势比（OR）和95%置信区间（CI）。对FAs合并MASLD进行孟德尔随机化（MR）分析，主分析采用方差反加权法。结果：在观察性分析中，我们发现了1500例MASLD。饱和脂肪酸（sfa）与MASLD风险呈正相关[ORQ3vsQ1: 2.41(95% CI: 1.56-3.74)]，而多不饱和脂肪酸（PUFAs）和omega-6 PUFAs呈负相关[ORQ3vsQ1: 0.49（0.30-0.80）和ORQ3vsQ1: 0.46(0.27-0.79)]。在30个FAs个体中，7个FAs与MASLD风险增加相关，其中二同型γ -亚麻酸风险最高[ORQ3vsQ1: 2.07(1.30-3.28)]。相反，3种脂肪酸呈负相关，亚油酸的风险最低[ORQ3vsQ1: 0.50(0.28-0.90)]。MR分析显示，基因预测的omega-6 PUFAs/总脂肪酸（TFA）[0.80(0.65-0.99)]、PUFAs/TFA[0.73(0.63-0.84)]与MASLD之间存在负因果关系。结论：个体FAs和集体脂肪酸类别与MASLD风险之间存在差异相关性，omega-6 PUFAs可能作为潜在预防和治疗MASLD的稳定生物标志物。

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来源期刊

Clinical nutrition ESPEN NUTRITION & DIETETICS-

CiteScore

4.90

自引率

3.30%

发文量

512

期刊介绍： Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.