ArticleBiochimica et biophysica acta. Molecular basis of disease2019
Dihomo-γ-linolenic acid inhibits several key cellular processes associated with atherosclerosis.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Comprehensive Integration of Genome-Wide Association and Gene Expression Studies Reveals Novel Gene Signatures and Potential Therapeutic Targets forFrontiers in immunology · 2021Pooled it
- Determinants of high-density lipoprotein (HDL) functions beyond proteome in Asian Indians: exploring the fatty acid profile of HDL phospholipids.Molecular and cellular biochemistry · 2022Trial
- Prospective clinical trial examining the impact of genetic variation in FADS1 on the metabolism of linoleic acid- and ɣ-linolenic acid-containing botanical oils.The American journal of clinical nutrition · 2020Trial
- AA in Rheumatoid Arthritis and Lupus.Reviews of physiology, biochemistry and pharmacology · 2027Review
- Blood multiomics reveal a dysregulated lipid mediator-mitochondrial network associated with the outcome of advanced cirrhosis.Nature communications · 2026Article
- Plasma metabolomics disentangles T2DM- and CAD-specific dysmetabolism and identifies potential biomarkers for CAD risk escalation in diabetic patients.Cardiovascular diabetology · 2025Article
- Extracorporeal photopheresis induces the release of anti-inflammatory fatty acids and oxylipins and suppresses pro-inflammatory sphingosine-1-phosphate.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- High levels of serum dihomo-γ-linolenic acid are associated with non-alcoholic fatty liver disease in type 2 diabetic patients.Diabetology international · 2025Article
- Free Fatty Acids and Complex Lipids in Patients With Severe Obesity Treated With Roux-En-Y Gastric Bypass: Impact of Diabetes Status.Biochemistry research international · 2025Article
- TRAP-Induced Platelet Reactivity Is Inhibited by Omega-3 Fatty Acid-Derived Prostaglandin E3 (PGE3).Biomedicines · 2024Article
- Atheroprotective Effect of Fucoidan in THP-1 Macrophages by Potential Upregulation of ABCA1.Biomedicines · 2023Article
- Anti-Atherogenic Actions of the Lab4b Consortium of Probiotics In Vitro.International journal of molecular sciences · 2023Article
- Dihomo-International journal of molecular sciences · 2023Review
- Punicalagin Targets Atherosclerosis: Gene Expression Profiling of THP-1 Macrophages Treated with Punicalagin and Molecular Docking.Current issues in molecular biology · 2022Article
- Anti-inflammatory and immunoregulatory effects of pinolenic acid in rheumatoid arthritis.Rheumatology (Oxford, England) · 2022Article
- Nutritional immunomodulation of Atlantic salmon response toFrontiers in molecular biosciences · 2022Article
- Macrophage-Mediated Immune Responses: From Fatty Acids to Oxylipins.Molecules (Basel, Switzerland) · 2021Review
- Effects of fatty acids on T cell function: role in atherosclerosis.Nature reviews. Cardiology · 2021Review
- Pro-atherogenic actions of signal transducer and activator of transcription 1 serine 727 phosphorylation in LDL receptor deficient mice via modulation of plaque inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The Lab4P Consortium of Probiotics Attenuates Atherosclerosis in LDL Receptor Deficient Mice Fed a High Fat Diet and Causes Plaque Stabilization by Inhibiting Inflammation and Several Pro-Atherogenic Processes.Molecular nutrition & food research · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Atherosclerosis and its complications are responsible for one in three global deaths. Nutraceuticals show promise in the prevention and treatment of atherosclerosis but require an indepth understanding of the mechanisms underlying their actions. A previous study showed that the omega-6 fatty acid, dihomo-γ-linolenic acid (DGLA), attenuated atherosclerosis in the apolipoprotein E deficient mouse model system. However, the mechanisms underlying such protective effects of DGLA are poorly understood and were therefore investigated. We show that DGLA attenuates chemokine-driven monocytic migration together with foam cell formation and the expression of key pro-atherogenic genes induced by three pro-inflammatory cytokines in human macrophages. The effect of DGLA on interferon-γ signaling was mediated via inhibition of signal transducer and activator of transcription-1 phosphorylation on serine 727. In relation to anti-foam cell action, DGLA inhibits modified LDL uptake by both macropinocytosis and receptor-mediated endocytosis, the latter by reduction in expression of two key scavenger receptors (SR-A and CD36), and stimulates cholesterol efflux from foam cells. DGLA also improves macrophage mitochondrial bioenergetic profile by decreasing proton leak. Gamma-linolenic acid and prostaglandin E1, upstream precursor and key metabolite respectively of DGLA, also acted in an anti-atherogenic manner. The actions of DGLA extended to other key atherosclerosis-associated cell types with attenuation of endothelial cell proliferation and migration of smooth muscle cells in response to platelet-derived growth factor. This study provides novel insights into the molecular mechanisms underlying the anti-atherogenic actions of DGLA and supports further assessments on its protective effects on plaque regression in vivo and in human trials.
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Registered trials
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.