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Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study

Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study
Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study
Background/Objective: Treatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (FAs) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial FA partitioning and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME trial (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy). Subjects/Methods: Sixteen participants were randomised to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15–18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or 2% post intervention). Results: Nine participants were stratified to DHA2% (eight randomised to EPA+DHA and one to placebo) and seven to the DHA<2% group (all placebo). Compared with individuals with erythrocyte <2% change in DHA abundance, those with 2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of 13C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05). Conclusions: The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment 2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.
0954-3007
973-978
Hodson, L.
0509c661-1bd1-427a-9dda-874db5d77be2
Bhatia, L.
41232d21-eef2-43a9-a129-994b81ccedaf
Scorletti, E.
42bb0659-ac67-4a73-bf36-a881fe6c1563
Smith, D.E.
b41c2f97-269c-4a50-ba95-830e823cc7df
Jackson, N.C.
c48f7c67-234a-4968-b017-c538f3790789
Shojaee-Moradie, F.
53eee249-e1cf-4501-8a58-d548bb2d537a
Umpleby, M.
c7097774-a5ea-4fe3-a29b-82cc1aa450fb
Calder, P.C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, C.D.
1370b997-cead-4229-83a7-53301ed2a43c
Hodson, L.
0509c661-1bd1-427a-9dda-874db5d77be2
Bhatia, L.
41232d21-eef2-43a9-a129-994b81ccedaf
Scorletti, E.
42bb0659-ac67-4a73-bf36-a881fe6c1563
Smith, D.E.
b41c2f97-269c-4a50-ba95-830e823cc7df
Jackson, N.C.
c48f7c67-234a-4968-b017-c538f3790789
Shojaee-Moradie, F.
53eee249-e1cf-4501-8a58-d548bb2d537a
Umpleby, M.
c7097774-a5ea-4fe3-a29b-82cc1aa450fb
Calder, P.C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Byrne, C.D.
1370b997-cead-4229-83a7-53301ed2a43c

Hodson, L., Bhatia, L., Scorletti, E., Smith, D.E., Jackson, N.C., Shojaee-Moradie, F., Umpleby, M., Calder, P.C. and Byrne, C.D. (2017) Docosahexaenoic acid enrichment in NAFLD is associated with improvements in hepatic metabolism and hepatic insulin sensitivity: a pilot study. European Journal of Clinical Nutrition, 71 (8), 973-978. (doi:10.1038/ejcn.2017.9).

Record type: Article

Abstract

Background/Objective: Treatment of subjects with non-alcoholic fatty liver disease (NAFLD) with omega-3 polyunsaturated fatty acids (FAs) suggests high levels of docosahexaenoic acid (DHA) tissue enrichment decrease liver fat content. We assessed whether changes in erythrocyte DHA enrichment (as a surrogate marker of changes in tissue enrichment) were associated with alterations in hepatic de novo lipogenesis (DNL), postprandial FA partitioning and hepatic and peripheral insulin sensitivity in a sub-study of the WELCOME trial (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD (non-alcoholic fatty liver disease) with OMacor thErapy). Subjects/Methods: Sixteen participants were randomised to 4 g/day EPA+DHA (n=8) or placebo (n=8) for 15–18 months and underwent pre- and post-intervention measurements. Fasting and postprandial hepatic FA metabolism was assessed using metabolic substrates labelled with stable-isotope tracers (2H2O and [U13C]palmitate). Insulin sensitivity was measured by a stepped hyperinsulinaemic-euglycaemic clamp using deuterated glucose. Participants were stratified according to change in DHA erythrocyte enrichment (< or 2% post intervention). Results: Nine participants were stratified to DHA2% (eight randomised to EPA+DHA and one to placebo) and seven to the DHA<2% group (all placebo). Compared with individuals with erythrocyte <2% change in DHA abundance, those with 2% enrichment had significant improvements in hepatic insulin sensitivity, reduced fasting and postprandial plasma triglyceride concentrations, decreased fasting hepatic DNL, as well as greater appearance of 13C from dietary fat into plasma 3-hydroxybutyrate (all P<0.05). Conclusions: The findings from our pilot study indicate that individuals who achieved a change in erythrocyte DHA enrichment 2% show favourable changes in hepatic FA metabolism and insulin sensitivity, which may contribute to decreasing hepatic fat content.

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Accepted/In Press date: 12 January 2017
e-pub ahead of print date: 15 March 2017
Published date: August 2017
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 404743
URI: http://eprints.soton.ac.uk/id/eprint/404743
ISSN: 0954-3007
PURE UUID: fa755f57-e709-4055-bf8f-3a1bc0def007
ORCID for P.C. Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for C.D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 20 Jan 2017 15:13
Last modified: 16 Mar 2024 03:08

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Contributors

Author: L. Hodson
Author: L. Bhatia
Author: E. Scorletti
Author: D.E. Smith
Author: N.C. Jackson
Author: F. Shojaee-Moradie
Author: M. Umpleby
Author: P.C. Calder ORCID iD
Author: C.D. Byrne ORCID iD

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