Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Lifestyle Genom. 2019;12(1-6):10-17. doi: 10.1159/000502008. Epub 2019 Aug 27.
BACKGROUND/AIMS: The PNPLA3 loss-of-function variant p.I148M is a strong genetic determinant of nonalcoholic fatty liver disease. The PNPLA3 protein functions as an intracellular lipase in the liver, with a greater activity on unsaturated fatty acids. This study aimed to determine whether short-term supplementation with omega-3 fatty acids impacts hepatic steatosis differently in PNPLA3 p.148I wild-type individuals as compared to homozygous carriers of the PNPLA3 p.148M variant.
Twenty subjects with hepatic steatosis (50% women, age 18-77 years) were included. Ten subjects homozygous for the PNPLA3 148M variant were matched to 10 wild-type individuals. The subjects received 4 g omega-3 fatty acids (1,840 mg eicosapentaenoic acid and 1,520 mg docosahexaenoic acid) a day for 4 weeks. Transient elastography with a controlled attenuation parameter (CAP) was used to quantify liver fat before and after the intervention. Body composition, fibrosis, liver function tests, serum free fatty acids (FFA) and glucose markers were compared.
Patients homozygous for the PNPLA3 p.148M variant (risk group) demonstrated no significant changes in CAP compared to baseline (284 ± 55 vs. 287 ± 65 dB/m) as did the control group (256 ± 56 vs. 262 ± 55 dB/m). While serum liver enzyme activities remained unchanged in both groups, the risk group displayed significantly (p = 0.02) lower baseline FFA concentrations (334.5 [range 281.0-431.0] vs. 564.5 [range 509.0-682.0] μmol/L), which markedly increased by 9.1% after the intervention. In contrast, FFA concentrations decreased significantly (p = 0.01) by 28.3% in the wild-type group.
Short-term omega-3 fatty acid supplementation did not significantly alter hepatic steatosis. The nutrigenomic and metabolic effects of omega-3 fatty acids should be investigated further in carriers of the PNPLA3 148M risk variant.
背景/目的：PNPLA3 无功能变异体 p.I148M 是导致非酒精性脂肪性肝病的一个强有力的遗传决定因素。PNPLA3 蛋白在肝脏中作为一种细胞内脂肪酶发挥作用，对不饱和脂肪酸的活性更高。本研究旨在确定与 PNPLA3 p.148M 变体的纯合子携带者相比，短期补充欧米伽-3 脂肪酸是否对 PNPLA3 p.148I 野生型个体的肝脂肪变性有不同的影响。
共纳入 20 例肝脂肪变性患者（50%为女性，年龄 18-77 岁）。10 例 PNPLA3 148M 变体纯合子患者与 10 例野生型个体相匹配。受试者每天接受 4 g 欧米伽-3 脂肪酸（1840 mg 二十碳五烯酸和 1520 mg 二十二碳六烯酸），干预 4 周。使用受控衰减参数（CAP）的瞬时弹性成像来量化干预前后的肝脏脂肪。比较身体成分、纤维化、肝功能试验、血清游离脂肪酸（FFA）和葡萄糖标志物。
与基线相比，PNPLA3 p.148M 变体纯合子患者（风险组）的 CAP 没有显著变化（284 ± 55 与 287 ± 65 dB/m），对照组也没有显著变化（256 ± 56 与 262 ± 55 dB/m）。虽然两组血清肝酶活性均保持不变，但风险组的基础 FFA 浓度显著降低（334.5[范围 281.0-431.0]与 564.5[范围 509.0-682.0]μmol/L），干预后 FFA 浓度显著增加 9.1%。相比之下，野生型组的 FFA 浓度显著降低 28.3%（p = 0.01）。
短期补充欧米伽-3 脂肪酸并未显著改变肝脂肪变性。PNPLA3 148M 风险变异携带者的欧米伽-3 脂肪酸的营养基因组和代谢作用需要进一步研究。
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