Four-Week Omega-3 Supplementation in Carriers of the Prosteatotic PNPLA3 p.I148M Genetic Variant: An Open-Label Study.
Adolescent
Adult
Aged
Amino Acid Substitution
/ genetics
Dietary Supplements
Elasticity Imaging Techniques
Fatty Acids, Omega-3
/ administration & dosage
Fatty Liver
/ diagnosis
Female
Genetic Predisposition to Disease
Heterozygote
Homozygote
Humans
Isoleucine
/ genetics
Lipase
/ genetics
Loss of Function Mutation
/ genetics
Male
Membrane Proteins
/ genetics
Methionine
/ genetics
Middle Aged
Non-alcoholic Fatty Liver Disease
/ diet therapy
Polymorphism, Single Nucleotide
Proteostasis
/ genetics
Time Factors
Young Adult
Elastography
Free fatty acids
Hepatic steatosis
Ketones
Nonalcoholic fatty liver disease
Journal
Lifestyle genomics
ISSN: 2504-3188
Titre abrégé: Lifestyle Genom
Pays: Switzerland
ID NLM: 101716139
Informations de publication
Date de publication:
2019
2019
Historique:
received:
21
05
2019
accepted:
08
07
2019
pubmed:
28
8
2019
medline:
26
8
2020
entrez:
28
8
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 31454802
pii: 000502008
doi: 10.1159/000502008
doi:
Substances chimiques
Fatty Acids, Omega-3
0
Membrane Proteins
0
Isoleucine
04Y7590D77
Methionine
AE28F7PNPL
Lipase
EC 3.1.1.3
adiponutrin, human
EC 3.1.1.3
Types de publication
Controlled Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10-17Informations de copyright
© 2019 S. Karger AG, Basel.