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

Artikel i vetenskaplig tidskrift
Författare C. S. Kuttner
Rosellina Margherita Mancina
G. Wagenpfeil
F. Lammert
C. S. Stokes
Publicerad i Lifestyle Genomics
Volym 12
Nummer/häfte 1-6
Sidor 10-17
ISSN 2504-3161
Publiceringsår 2019
Publicerad vid Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 10-17
Språk en
Länkar dx.doi.org/10.1159/000502008
Ämnesord Elastography, Free fatty acids, Hepatic steatosis, Ketones, Nonalcoholic, fatty liver disease, fatty liver-disease, i148m variant, acid, susceptibility, polymorphism, fibrosis, risk, diet, Genetics & Heredity, Nutrition & Dietetics
Ämneskategorier Näringslära, Medicinsk genetik

Sammanfattning

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.

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