Intestinal ABCA1 directly contributes to HDL biogenesis in vivo
Open accessAbstract
Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. The liver is known to be the major source of plasma HDL, but it is likely that there are other important sites of HDL biogenesis. To assess the contribution of intestinal ABCA1 to plasma HDL levels in vivo, we generated mice that specifically lack ABCA1 in the intestine. Our results indicate that approximately 30% of the steady-state plasma HDL pool is contributed by intestinal ABCA1 in mice. In addition, our data suggest that HDL derived from intestinal ABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment. These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ABCA1-mediated cholesterol export is essential for the formation of HDL particles, because liver- and intestine-specific ABCA1 knockout mice show strong reductions in HDL levels.
“This process seems to be essential for the formation of HDL particles because liver-and intestine-specific knockout mice for ABCA1 show strong reductions in HDL levels (45)(46)(47).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Increased ABCA1 activity protects against atherosclerosis
Singaraja, R. R., Fievet, C., Castro, G., James, E. R., Hennuyer, N., Clee, S. M., Bissada, N., Choy, J. C., Fruchart, J.-C., McManus, B. M., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15748 · Cited by 250 · see citing works
Cholesterol and apolipoprotein B metabolism in Tangier disease
Schaefer, E. J., Brousseau, M. E., Diffenderfer, M. R., Cohn, J. S., Welty, F. K., O'Connor, J., Dolnikowski, G. G., Wang, J., Hegele, R. A., & Jones, P. J. (2001) · Atherosclerosis · doi:10.1016/s0021-9150(01)00688-8 · Cited by 52 · cited 2× · see citing works
“However, this is unlikely to be the sole mechanism, since patients with apoA-I deficiency also lack plasma HDL cholesterol but do not exhibit the reduction in LDL cholesterol observed in Tangier disease (64), and mice that lack ABCA1 globally or in the liver have reduced LDL cholesterol but do not have CETP (16, 41).”
Background
Flagged first, then by citations
Research works printed but not linked: 8
- Timmins, J.M., et al. 2005. Targeted inactivation of hepatic Abca1 causes profound hypoalphali- poproteinemia and kidney hypercatabolism of apoA-I. J. Clin. Invest. 115:1333-1342. doi:10.1172/ JCI200523915. · DOI · Paper page
- Stange, E.F., and Dietschy, J.M. 1983. Cholesterol syn- thesis and low density lipoprotein uptake are regulat- ed independently in rat small intestinal epithelium. Proc. Natl. Acad. Sci. U. S. A. 80:5739-5743.
- Farrell, J.J. 2002. Digestion and absorption of nutri- ents and vitamins. In Sleisenger and Fordtran's gastro- intestinal and liver disease. M. Feldman, L. Friedman, and M. Sleisenger, editors. Saunders. Philadelphia, Pennsylvania, USA. 1715-1750.
- Assmann, G., von Eckardstein, A., and Brewer, H.B. 1995. Familial high density lipoprotein deficiency: Tangier disease. In The metabolic and molecular bases of inherited disease. C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle, editors. McGraw Hill Inc. New York, New York, USA. 2053-2072.
- McNeish, J., et al. 2000. High density lipoprotein defi- ciency and foam cell accumulation in mice with target- ed disruption of ATP-binding cassette transporter-1. Proc. Natl. Acad. Sci. U. S. A. 97:4245-4250.
- Glickman, R.M., and Green, P.H. 1977. The intes- tine as a source of apolipoprotein A1. Proc. Natl. Acad. Sci. U. S. A. 74:2569-2573.
- Vaisman, B.L., et al. 2001. ABCA1 overexpres- sion leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice. J. Clin. Invest. 108:303-309. doi:10.1172/ JCI200112517. · DOI
- Breslow, J.L. 1995. Familial disorders of high-den- sity lipoprotein metabolism. In The metabolic and molecular bases of inherited disease. C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle, editors. McGraw Hill Inc. New York, New York, USA. 2031-2052.
Cited by
Sorted by citations
Cholesterol Efflux and Atheroprotection: Advancing the Concept of Reverse Cholesterol Transport
Rosenson, R. S., Brewer, H. B., Davidson, W. S., Fayad, Z. A., Fuster, V., Goldstein, J., Hellerstein, M., Jiang, X.-C., Phillips, M. C., Rader, D. J., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.066589 · Cited by 953 · see citing works
Iqbal, J., & Hussain, M. M. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90899.2008 · Cited by 811 · see citing works
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722 · see citing works
Regulation of intestinal lipid metabolism: current concepts and relevance to disease
Ko, C.-W., Qu, J., Black, D. D., & Tso, P. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0250-7 · Cited by 510 · see citing works
Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation*
Gerin, I., Clerbaux, L.-A., Haumont, O., Lanthier, N., Das, A. K., Burant, C. F., Leclercq, I. A., MacDougald, O. A., & Bommer, G. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152090 · Cited by 382 · see citing works
Zhu, X., Owen, J. S., Wilson, M. D., Li, H., Griffiths, G. L., Thomas, M. J., Hiltbold, E. M., Fessler, M. B., & Parks, J. S. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m006486 · Cited by 331 · see citing works
Hegele, R. A., Borén, J., Ginsberg, H. N., Arca, M., Averna, M., Binder, C. J., Calabresi, L., Chapman, M. J., Cuchel, M., von Eckardstein, A., et al. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30264-5 · Cited by 204 · see citing works
DUVAL, C., MULLER, M., & KERSTEN, S. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2007.05.003 · Cited by 199 · see citing works
New insights into the regulation of chylomicron production
Dash, S., Xiao, C., Morgantini, C., & Lewis, G. F. (2015) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071714-034338 · Cited by 194 · see citing works
Cholesterol in islet dysfunction and type 2 diabetes
Brunham, L. R., Kruit, J. K., Verchere, C. B., & Hayden, M. R. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33296 · Cited by 158 · see citing works
Self-citationNovel HDL-directed pharmacotherapeutic strategies
deGoma, E. M., & Rader, D. J. (2011) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.200 · Cited by 149 · see citing works
Nazir, S., Jankowski, V., Bender, G., Zewinger, S., Rye, K.-A., & van der Vorst, E. P. C. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.10.006 · Cited by 140 · see citing works
New insights into the mechanism of low high-density lipoprotein cholesterol in obesity
Wang, H., & Peng, D.-Q. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-176 · Cited by 140 · see citing works
Liver X receptors (LXR) as therapeutic targets in dyslipidemia
Bełtowski, J. (2008) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2008.00062.x · Cited by 132 · see citing works
Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism
Gnocchi, D., Pedrelli, M., Hurt-Camejo, E., & Parini, P. (2015) · Biology · doi:10.3390/biology4010104 · Cited by 115 · see citing works
Tissue-Specific Roles of ABCA1 Influence Susceptibility to Atherosclerosis
Brunham, L. R., Singaraja, R. R., Duong, M., Timmins, J. M., Fievet, C., Bissada, N., Kang, M. H., Samra, A., Fruchart, J.-C., McManus, B., et al. (2009) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.182303 · Cited by 102 · see citing works
Self-citationTreadmill exercise enhances ABCA1 expression in rat liver
Ghanbari-Niaki, A., Khabazian, B. M., Hossaini-Kakhak, S. A., Rahbarizadeh, F., & Hedayati, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.100 · Cited by 94 · see citing works
High-density lipoprotein (HDL) metabolism and bone mass
Papachristou, N. I., Blair, H. C., Kypreos, K. E., & Papachristou, D. J. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0657 · Cited by 94 · see citing works
Hepatic ABCA1 and VLDL triglyceride production
Liu, M., Chung, S., Shelness, G. S., & Parks, J. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.09.020 · Cited by 43 · see citing works
Takei, K., Nakagawa, Y., Wang, Y., Han, S.-I., Satoh, A., Sekiya, M., Matsuzaka, T., & Shimano, H. (2017) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2017.02.003 · Cited by 43 · see citing works
- Authors
- Brunham, L. R.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Brunham, L. R.
- ORCID
- Brunham, L. R.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-03-23
- Volume
- 116
- Issue
- 4
- Pages
- 1052-1062
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1401485
- OpenAlex
- W2167612600
- Cited by
- 519
- References
- 3
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 11 · 2023: 16 · 2022: 14 · 2021: 14 · 2020: 28 · 2019: 26 · 2018: 22 · 2017: 23 · 2016: 24 · 2015: 22 · 2014: 37 · 2013: 35 · 2012: 35
- FWCI
- 37.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- National Institutes of Health (DK-46900)
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (HL 49373, HL 07115, R01HL064272, T32HL007115, HL-64272, P01HL049373)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK046900, DK-46900, R56DK046900, R29DK046900)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- ABCA1, HDL biogenesis, HDL cholesterol, apolipoprotein A-I, free cholesterol, phospholipids, atherosclerosis
- MeSH terms
- Animals, Fluorescent Antibody Technique, Intestinal Mucosa, Intestines, Cholesterol, HDL, Lymph, Mice, Inbred C57BL, Mice, Transgenic, Mice, Knockout, ATP-Binding Cassette Transporters, Mice, ATP Binding Cassette Transporter 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
