Liu Zhibing, Wang Peng, Wang Yiming, Yu Jing, Wang Qingxuan, Li Jibin, Shi Dan
Department of Nutrition and Food Hygiene, School of Public Health, Chongqing Medical University, Chongqing, China; Research Centre for Environment and Human Health, School of Public Health, Chongqing Medical University, Chongqing, China.
Department of Nutrition Food and Children's Health, School of Public Health, Shandong Second Medical University, Weifang, China.
Clin Nutr ESPEN. 2025 Oct;69:294-302. doi: 10.1016/j.clnesp.2025.07.027. Epub 2025 Jul 16.
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.
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.
In observational analysis, we identified 1500 cases of MASLD. Saturated FAs (SFAs) were positively associated with MASLD risk [OR: 2.41 (95 % CI: 1.56-3.74)], whereas polyunsaturated FAs (PUFAs) and omega-6 PUFAs showed the negative associations [OR: 0.49 (0.30-0.80) and OR: 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: 2.07 (1.30-3.28)]. In contrast, 3 FAs showed an inverse association, with the lowest risk observed for linoleic acid [OR: 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.
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.
代谢功能障碍相关脂肪性肝病（MASLD）是一种普遍存在的疾病，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。本研究旨在阐明脂肪酸与MASLD之间的关联。
本研究分析了2011 - 2014年美国国家健康与营养检查调查的数据，包括3084名有血清脂肪酸浓度（占总脂肪酸的百分比）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风险的比值比（OR）和95%置信区间（CI）。对脂肪酸与MASLD进行孟德尔随机化（MR）分析，主要分析采用逆方差加权法。
在观察性分析中，我们确定了1500例MASLD病例。饱和脂肪酸（SFAs）与MASLD风险呈正相关[OR：2.41（95%CI：1.56 - 3.74）]，而多不饱和脂肪酸（PUFAs）和ω-6多不饱和脂肪酸呈负相关[分别为OR：0.49（0.30 - 0.80）和OR：0.46（0.27 - 0.79）]。在30种个体脂肪酸中，7种与MASLD风险增加相关，二高-γ-亚麻酸风险最高[OR：2.07（1.30 - 3.28）]。相反，3种脂肪酸呈负相关，亚油酸风险最低[OR：0.50（0.28 - 0.90）]。MR分析揭示了基因预测的ω-6多不饱和脂肪酸/总脂肪酸（TFA）[OR：0.80（0.65 - 0.99）]、多不饱和脂肪酸/总脂肪酸（TFA）[OR：0.73（0.63 - 0.84）]与MASLD之间的负因果关系。
个体脂肪酸和集体脂肪酸类别与MASLD风险之间存在差异关联，ω-6多不饱和脂肪酸可能作为MASLD潜在预防和治疗的稳定生物标志物。
