Down-regulation of the low-density lipoprotein receptor by dietary cholesterol
Abstract
To determine the effect of dietary cholesterol on the low-density lipoprotein (LDL) receptor of circulating mononuclear cells, nine adults (six men, three women) consumed a natural diet consisting of 45% of the calories as carbohydrate, 40% as fat, and 15% as protein, polyunsaturated/saturated fatty acid ratio 0.80 to 0.84, and either 137 +/- 25 mg cholesterol per day (low cholesterol phase) or 1034 +/- 25 mg cholesterol per day (high cholesterol phase). The study lasted 2 months with 1 month in each phase and used a cross-over design. The levels of plasma triglyceride, plasma cholesterol, very low-density and high-density lipoprotein cholesterol, and apolipoproteins B, A-I, and A-II were similar in the two diet phases. The high cholesterol diet was associated with an 11 +/- 9% increase (p less than 0.02) in LDL cholesterol level and a 41 +/- 14% decrease in LDL receptor activity (p less than 0.05, n = 6). The percentage decrease in LDL receptor activity correlated with the percentage increase in LDL cholesterol (r = -0.796, p = 0.06, n = 6). Thus, high levels of dietary cholesterol can down-regulate the LDL receptor in humans.
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Numerous 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 [3]
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 [3]
Cites
PLASMA-HIGH-DENSITY-LIPOPROTEIN CONCENTRATION AND DEVELOPMENT OF ISCHÆMIC HEART-DISEASE
Miller, G. J., & Miller, N. E. (1975) · The Lancet · doi:10.1016/s0140-6736(75)92376-4 · Cited by 2,621 · see citing works
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A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Weggemans, R. M., Zock, P. L., & Katan, M. B. (2001) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/73.5.885 · Cited by 333 · see citing works
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
- D, A.-B., S M, H., E, H., K H, L., J J, A., & W R, H.
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 1984-03
- Volume
- 39
- Issue
- 3
- Pages
- 360-367
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2149637110
- Cited by
- 85
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 2 · 2020: 3 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- dietary cholesterol, LDL receptor, receptor down-regulation, LDL cholesterol, high-cholesterol diet, mononuclear cells, plasma lipids, apolipoproteins, dietary fat
- MeSH terms
- Adult, Apolipoproteins, Energy Intake, Cholesterol, Cholesterol, Dietary, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Female, Humans, Lipoproteins, Male, Receptors, Cell Surface, Receptors, LDL, Triglycerides
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