ArticleThe Journal of biological chemistry2015
Excess Linoleic Acid Increases Collagen I/III Ratio and "Stiffens" the Heart Muscle Following High Fat Diets.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- From bump to pump: extracellular matrix remodeling, dynamics, and biomechanics in the maternal heart.American journal of physiology. Heart and circulatory physiology · 2026Review
- Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Short-Term Oral Administration of the Porcupine Inhibitor, Wnt-c59, Improves the Structural and Functional Features of Experimental HFpEF.Pharmacology research & perspectives · 2025Article
- The role of collagen and collagen I/III ratio in pathological conditions: insights into molecular mechanisms and therapeutic approaches.Frontiers in bioengineering and biotechnology · 2025Review
- Decelerated skin aging effect of rubber (Hevea brasiliensis) seed oil in cell culture assays.Scientific reports · 2024Article
- Fatty acid composition, lipid profile and oxidative stability of meat of broiler chickens fed diet containing bird eye pepper of varying inclusion level and sieve size.Tropical animal health and production · 2024Article
- Red blood cell exposure increases chondrocyte susceptibility to oxidative stress following hemarthrosis.Osteoarthritis and cartilage · 2023Article
- The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure.The journal of cardiovascular aging · 2023Article
- Distinctive structure, composition and biomechanics of collagen fibrils in vaginal wall connective tissues associated with pelvic organ prolapse.Acta biomaterialia · 2022Article
- The FADS1 genotypes modify the effect of linoleic acid-enriched diet on adipose tissue inflammation via pro-inflammatory eicosanoid metabolism.European journal of nutrition · 2022Article
- Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling.World journal of gastroenterology · 2021Article
- Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite-Protein Interaction Network.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Review
- Extracellular Matrix Biomarkers in Colorectal Cancer.International journal of molecular sciences · 2021Review
- Article
- Effects of Three-Month Feeding High Fat Diets with Different Fatty Acid Composition on Myocardial Proteome in Mice.Nutrients · 2021Article
- Analysis of Colorectal Carcinogenesis Paradigm between Cold Constitution and Heat Constitution: Earlier ECM Collagen Deposition.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis.Oncology reports · 2020Article
- Review
- Obesogenic diet in aging mice disrupts gut microbe composition and alters neutrophil:lymphocyte ratio, leading to inflamed milieu in acute heart failure.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Controversy exists on the benefits versus harms of n-6 polyunsaturated fatty acids (n-6 PUFA). Although n-6 PUFA demonstrates anti-atherosclerotic properties, survival following cardiac remodeling may be compromised. We hypothesized that n-6 PUFA like linoleic acid (LA) or other downstream PUFAs like γ-linolenic acid or arachidonic acid alter the transforming growth factor-β (TGFβ)-collagen axis in the heart. Excess dietary LA increased the collagen I/III ratio in the mouse myocardium, leading to cardiac "stiffening" characterized by impaired transmitral flow indicative of early diastolic dysfunction within 5 weeks. In vitro, LA under TGFβ1 stimulation increased collagen I and lysyl oxidase (LOX), the enzyme that cross-links soluble collagen resulting in deposited collagen. Overexpression of fatty acid desaturase 2 (fads2), which metabolizes LA to downstream PUFAs, reduced collagen deposits, LOX maturation, and activity with LA, whereas overexpressing fads1, unrelated to LA desaturation, did not. Furthermore, fads2 knockdown by RNAi elevated LOX activity and collagen deposits in fibroblasts with LA but not oleic acid, implying a buildup of LA for aggravating such pro-fibrotic effects. As direct incubation with γ-linolenic acid or arachidonic acid also attenuated collagen deposits and LOX activity, we concluded that LA itself, independent of other downstream PUFAs, promotes the pro-fibrotic effects of n-6 PUFA. Overall, these results attempt to reconcile opposing views of n-6 PUFA on the cardiovascular system and present evidence supporting a cardiac muscle-specific effect of n-6 PUFAs. Therefore, aggravation of the collagen I/III ratio and cardiac stiffening by excess n-6 PUFA represent a novel pathway of cardiac lipotoxicity caused by high n-6 PUFA diets.
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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.