Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.
Division of Pediatric Gastrointestinal Diseases, Hepatology, and Nutrition, University of California San Diego, San Diego, CA, USA.
J Nutr. 2020 Sep 1;150(9):2314-2321. doi: 10.1093/jn/nxaa183.
Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth.
We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response.
In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used.
Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time.
These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.
最近的文献表明，西方饮食中ω-6（n-6）与ω-3（n-3）多不饱和脂肪酸摄入比例的失衡导致肥胖青少年发生脂肪肝。
我们旨在检验低脂 n-6:n-3 多不饱和脂肪酸（PUFA）比值（4:1）的 12 周常规热量饮食是否可以减轻脂肪肝，以及载脂蛋白样磷脂酶 3（PNPLA3）rs738409 变异是否会影响治疗反应。
在一项单臂、非盲研究中，患有非酒精性脂肪性肝病的肥胖青少年（9-19 岁）接受了为期 12 周的低 n-6:n-3 PUFA 比值常规热量饮食治疗。主要结局是通过腹部 MRI 测量肝脂肪分数（HFF%）的变化。代谢参数包括丙氨酸氨基转移酶（ALT）、血脂、胰岛素敏感性测量指标和血浆氧化亚油酸代谢物（OXLAMs）。还根据 PNPLA3 rs738409 基因型分析了结局。采用 Wilcoxon 符号秩检验、Mann-Whitney U 检验和协方差模式建模。
共纳入 20 名肥胖青少年（中位年龄：13.3 岁；IQR：10.5-16.4 岁），其中 17 人完成了研究。尽管体重稳定，但在接受 12 周饮食干预后，HFF%降低了 25.8%（P = 0.009）。我们观察到 ALT 降低了 34.4%（P = 0.001）、甘油三酯降低了 21.9%（P = 0.046）、LDL 胆固醇降低了 3.28%（P = 0.071），全身胰岛素敏感性提高了 26.3%（P = 0.032）。9-羟基十八碳烯酸（9-HODE）（P = 0.011）、13-羟基十八碳烯酸（13-HODE）（P = 0.007）和 9-氧代十八碳二烯酸（9-oxoODE）（P = 0.024）在 12 周后下降。在非风险（CC/CG）和风险（GG）PNPLA3 rs738409 基因型组中，HFF%均降低，且 GG 基因型组 HFF%显著降低（P = 0.016）。9-HODE（P = 0.023）、9-oxoODE（P = 0.009）和 13-oxoODE（P = 0.003）的变化在两组间存在时间差异。
这些数据表明，低 n-6:n-3 PUFA 饮食可改善青少年脂肪肝的代谢表型，且这种饮食的反应受 PNPLA3 rs738409 基因型的调节，这种作用独立于体重减轻。本研究在 clinicaltrials.gov 上注册为 NCT01556113。
