A Null Mutation in Murine CD36 Reveals an Important Role in Fatty Acid and Lipoprotein Metabolism
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A null mutation in the scavenger receptor gene CD36 was created in mice by targeted homologous recombination. These mice produced no detectable CD36 protein, were viable, and bred normally. A significant decrease in binding and uptake of oxidized low density lipoprotein was observed in peritoneal macrophages of null mice as compared with those from control mice. CD36 null animals had a significant increase in fasting levels of cholesterol, nonesterified free fatty acids, and triacylglycerol. The increase in cholesterol was mainly within the high density lipoprotein fraction, while the increase in triacylglycerol was within the very low density lipoprotein fraction. Null animals had lower fasting serum glucose levels when compared with wild type controls. Uptake of 3H-labeled oleate was significantly reduced in adipocytes from null mice. However, the decrease was limited to the low ratios of fatty acid:bovine serum albumin, suggesting that CD36 was necessary for the high affinity component of the uptake process. The data provide evidence for a functional role for CD36 in lipoprotein/fatty acid metabolism that was previously underappreciated.
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CD36 has an important role in long-chain fatty acid uptake into skeletal muscle in rodents and humans, and its concentration and activity increase after exercise.
“There is abundant evidence which indicates that CD36 plays an important role in LCFA uptake into skeletal muscle in rodents and human and its concentration and activity are increased following exercise [89–96].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [91]
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- Authors
- Febbraio, M., Abumrad, N. A., Hajjar, D. P., Sharma, K., Cheng, W., Pearce, S. F. A., & Silverstein, R. L.
- Affiliations
- Cornell University (US)
- State University of New York (US)
- Corresponding author
- Febbraio, Maria
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-07
- Volume
- 274
- Issue
- 27
- Pages
- 19055-19062
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2058194924
- Cited by
- 769
- References
- 97
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 8 · 2023: 16 · 2022: 12 · 2021: 25 · 2020: 23 · 2019: 16 · 2018: 26 · 2017: 19 · 2016: 22 · 2015: 24 · 2014: 26 · 2013: 27 · 2012: 34
- FWCI
- 48.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r29hl058559-01a1, 5p50hl056987-05, 5r01hl042540-09, HL56987)
- National Heart, Lung, and Blood Institute (2R01 HL42540, 1R29 HL58559-01A1, 1P0 HL56987)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- CD36, scavenger receptors, null mutations, fatty acid uptake, lipoprotein metabolism, oxidized LDL uptake, peritoneal macrophages, cholesterol, triglycerides, VLDL, high-density lipoprotein, serum glucose, oleate uptake, adipocytes, knockout mice
- MeSH terms
- Animals, Blood Glucose, Cells, Cultured, Cholesterol, Fatty Acids, Fatty Acids, Nonesterified, Female, Lipoproteins, LDL, Male, Mice, Inbred C57BL, Mutation, Triglycerides, Adipocytes, Mice, Knockout, CD36 Antigens, Mice
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