Evidence map›Paper›PMID 40699986›Full record

ArticleThe Biochemical journal2025

Pharmaco-nutraceutical improvement of the response to obeticholic acid with omega-3 polyunsaturated fatty acids.

Audrey-Anne Lavoie, Ariane Thérien, Anisia Silva, Emanuel Paré, Anna Ciešlak, William Gagnon, Clémence Desjardins, Mélanie Verreault, Jocelyn Trottier, Marie-Claude Vohl and 4 more

Abstract read
In one paragraph

Article in The Biochemical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Audrey-Anne Lavoie *Laboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
Ariane Thérien *Laboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
Anisia SilvaFaculty of Pharmacy, Université Laval, Québec, QC G1V 0A6, Canada.
Emanuel ParéCHU de Québec Research Center, Université Laval, Québec, QC G1V 4G5, Canada.
Anna CiešlakLaboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
William GagnonLaboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
Clémence DesjardinsLaboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
Mélanie VerreaultLaboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
Jocelyn TrottierLaboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.
Marie-Claude VohlCentre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.
Jean-Philippe Drouin-ChartierCentre Nutrition, santé et société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec, QC G1V 0A6, Canada.
Jacques CorbeilCHU de Québec Research Center, Université Laval, Québec, QC G1V 4G5, Canada.
Alexandre CaronFaculty of Pharmacy, Université Laval, Québec, QC G1V 0A6, Canada.
Olivier BarbierLaboratory of Molecular Pharmacology, Endocrinology-Nephrology, CHU de Québec Research Center, Québec, QC G1V 4G2, Canada.ORCID 0000-0002-3067-1134

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Obeticholic acid (OCA) is the second-line therapy for primary biliary cholangitis. While efficient in promoting bile acid (BA) detoxification and limiting liver fibrosis, its clinical use is restricted by severe dose-dependent side effects. We tested the hypothesis that adding n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids to OCA may improve the therapeutic effect of the low drug dosage. Several liver cell lines were exposed to vehicle, low or high OCA dose (1-20 μM) in the presence or absence of EPA/DHA for 24 h. To induce ER stress, apoptosis, and fibrosis, HepG2 cells were exposed to a 400 μM BA mixture or to 2 ng/ml transforming growth factor-β (TGF-β). For inflammation analyses, THP-1 cells were activated with 100 ng/ml lipopolysaccharides (LPS). The impact of OCA+EPA/DHA was assessed using transcriptomic (qRT-PCR), proteomic (ELISA, caspase-3), and metabolomic (LC-MS/MS) approaches. The addition of EPA/DHA reinforced the ability of low OCA dose to down-regulate the expression of genes involved in BA synthesis (CYP7A1 and CYP8B1) and uptake (NTCP) and to up-regulate the expression of MRP2 and 3 genes. EPA/DHA also enhanced the anti-inflammatory response of the drug by reducing the expression of the LPS-induced cytokines: tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-1β, and monocyte chemoattractant protein-1 in THP-1 macrophages. OCA+EPA/DHA decreased the expression of BIP, CHOP, and COL1A1 genes and the caspase-3 activity. EPA+DHA potentiate the response to low OCA doses on BA toxicity and provide additional benefits on ER stress, apoptosis, inflammation, and fibrosis. These observations support the idea that adding n-3 PUFAs to the drug may reduce the risk of dose-related side effects in patients treated with OCA.

Indexed as

Chenodeoxycholic AcidDietary SupplementsDocosahexaenoic AcidsEicosapentaenoic AcidFatty Acids, Omega-3ApoptosisEndoplasmic Reticulum StressHep G2 CellsHumansMultidrug Resistance-Associated Protein 2THP-1 CellsABCC2 protein, humanChenodeoxycholic AcidDocosahexaenoic AcidsEicosapentaenoic AcidFatty Acids, Omega-3Multidrug Resistance-Associated Protein 2obeticholic acidautoimmune liver diseasesbile acid detoxificationdrug response improvementinflammation and fibrosis resolutionn-3 polyunsaturated fatty acids

Identifiers

PMID40699986
PMCPMC12493161

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.