Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.
Open accessAbstract
The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid-induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level.
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The molecular switches that coordinate LDLR trafficking and turnover in response to nutritional cues, including high dietary cholesterol, remain poorly defined.
“The molecular switches that coordinate LDLR trafficking and turnover in response to nutritional cues, including high dietary cholesterol, remain poorly defined 3-6 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [5]
The Discussion (page not provided) says the mechanism by which dietary fatty acids regulate LDL receptor mRNA is unknown. But the Introduction and Discussion describe an established sterol-responsive mechanism for LDL receptor gene transcription. The paper does not establish that the molecular switches governing LDLR trafficking and turnover in response to high dietary cholesterol remain poorly defined. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNumerous studies have shown that dietary cholesterol produces a marked reduction in hepatic LDLR levels.
“Numerous studies have shown that dietary cholesterol produces a marked reduction in hepatic LDLR levels 3-6 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [5]
The Results report that dietary cholesterol reduced hepatic LDL receptor protein in hamsters, markedly so with coconut oil: levels fell to 52% and 36% of control at the two cholesterol doses. With safflower oil, levels remained at 93% and 80%, so the claim overstates the reduction by omitting its dependence on dietary fat. (LLM, conf=0.86)
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Cites
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Kong, W., Wei, J., Abidi, P., Lin, M., Inaba, S., Li, C., Wang, Y., Wang, Z., Si, S., Pan, H., et al. (2004) · Nature Medicine · doi:10.1038/nm1135 · Cited by 1,391 · see citing works
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Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover
Feng, X., Zhang, S., Wang, Y., Kurlagunda, T., Sit, A., Jaishankar, P., Yang, P., Sakane, S., Park, S. Y., Wisessaowapak, C., et al. (2026) · Nature · doi:10.1038/s41586-026-10697-z · Cited by 2 · see citing works
- Authors
- Horton, J. D., Cuthbert, J. A., & Spady, D. K.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-08-01
- Volume
- 92
- Issue
- 2
- Pages
- 743-749
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC294909
- OpenAlex
- W2086388293
- Cited by
- 100
- References
- 1
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health (AM07100)
- National Heart, Lung, and Blood Institute (HL38409, R01HL038409)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- dietary fatty acids, LDL receptor, LDL receptor mRNA, safflower oil, coconut oil, dietary cholesterol, hamster, gene expression regulation
- MeSH terms
- Coconut Oil, Animals, Base Sequence, Biological Transport, Cholesterol, Dietary, Dietary Fats, Fatty Acids, Glyceraldehyde-3-Phosphate Dehydrogenases, Cricetinae, Kinetics, Lipoproteins, LDL, Cholesterol, LDL, Liver, Male, Mesocricetus, Molecular Sequence Data, Oligodeoxyribonucleotides, Plant Oils, Receptors, LDL, RNA, Messenger, Safflower Oil, Polymerase Chain Reaction
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