Four-Week Omega-3 Supplementation in Carriers of the Prosteatotic PNPLA3 p.I148M Genetic Variant: An Open-Label Study

IF 2 4区 医学 Q3 GENETICS & HEREDITY
C. Kuttner, R. Mancina, G. Wagenpfeil, F. Lammert, C. Stokes
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引用次数: 3

Abstract

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. Methods: 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. Results: 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. Conclusions: 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.
前列腺癌PNPLA3 p.I148M基因变异携带者补充四周Omega-3:一项开放标签研究
背景/目的:PNPLA3功能丧失变体p.I148M是非酒精性脂肪肝的一个强大的遗传决定因素。PNPLA3蛋白在肝脏中起细胞内脂肪酶的作用,对不饱和脂肪酸具有较大的活性。本研究旨在确定短期补充omega-3脂肪酸对pnpla3p . 148i野生型个体的肝脏脂肪变性的影响是否与pnpla3p . 148m变体纯合携带者不同。方法:纳入20例肝脂肪变性患者(50%为女性,年龄18-77岁)。10个PNPLA3 148M变异纯合子与10个野生型个体匹配。受试者每天服用4 g omega-3脂肪酸(1,840 mg二十碳五烯酸和1,520 mg二十二碳六烯酸),持续4周。采用控制衰减参数的瞬时弹性成像(CAP)来量化干预前后的肝脏脂肪。比较体成分、纤维化、肝功能、血清游离脂肪酸(FFA)和血糖指标。结果:纯合子PNPLA3 p.148M变异的患者(风险组)与基线(284±55比287±65 dB/m)和对照组(256±56比262±55 dB/m)相比,CAP没有显著变化。两组的血清肝酶活性保持不变,但危险组的基线FFA浓度显著(p = 0.02)降低(334.5 μmol/L[范围281.0-431.0]vs. 564.5 μmol/L[范围509.0-682.0]),干预后显著升高9.1%。相比之下,野生型组FFA浓度显著下降28.3% (p = 0.01)。结论:短期补充omega-3脂肪酸不会显著改变肝脏脂肪变性。omega-3脂肪酸对PNPLA3 148M风险变异携带者的营养基因组学和代谢影响有待进一步研究。
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来源期刊
Lifestyle Genomics
Lifestyle Genomics Agricultural and Biological Sciences-Food Science
CiteScore
4.00
自引率
7.70%
发文量
11
审稿时长
28 weeks
期刊介绍: Lifestyle Genomics aims to provide a forum for highlighting new advances in the broad area of lifestyle-gene interactions and their influence on health and disease. The journal welcomes novel contributions that investigate how genetics may influence a person’s response to lifestyle factors, such as diet and nutrition, natural health products, physical activity, and sleep, amongst others. Additionally, contributions examining how lifestyle factors influence the expression/abundance of genes, proteins and metabolites in cell and animal models as well as in humans are also of interest. The journal will publish high-quality original research papers, brief research communications, reviews outlining timely advances in the field, and brief research methods pertaining to lifestyle genomics. It will also include a unique section under the heading “Market Place” presenting articles of companies active in the area of lifestyle genomics. Research articles will undergo rigorous scientific as well as statistical/bioinformatic review to ensure excellence.
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