PUBLICATION
ω-6 (18:2) and ω-3 (18:3) fatty acids in reconstituted high-density lipoproteins show different functionality of anti-atherosclerotic properties and embryo toxicity
- Authors
- Park, K.H., Kim, J.Y., Choi, I., Kim, J.R., Cho, K.H.
- ID
- ZDB-PUB-150914-2
- Date
- 2015
- Source
- The Journal of Nutritional Biochemistry 26(12): 1613-21 (Journal)
- Registered Authors
- Keywords
- Atherosclerosis, Inflammation, Linoleic acid (ω-6), Linolenic acid (ω-3), Reconstituted HDL, Zebrafish
- MeSH Terms
-
- Animals
- Antioxidants/chemistry
- Apolipoprotein A-I/metabolism
- Atherosclerosis/metabolism*
- Atherosclerosis/prevention & control*
- Cellular Senescence
- Circular Dichroism
- Fibroblasts/cytology
- Gene Expression Regulation, Developmental
- Humans
- Inflammation
- Linoleic Acid/chemistry*
- Lipids/chemistry
- Lipoproteins, HDL/chemistry*
- Lipoproteins, LDL/chemistry
- Macrophages/metabolism
- Oxygen/chemistry
- Phagocytosis
- Reactive Oxygen Species/metabolism
- Tryptophan/chemistry
- Zebrafish
- alpha-Linolenic Acid/chemistry*
- PubMed
- 26363928 Full text @ J. Nutr. Biochem.
Citation
Park, K.H., Kim, J.Y., Choi, I., Kim, J.R., Cho, K.H. (2015) ω-6 (18:2) and ω-3 (18:3) fatty acids in reconstituted high-density lipoproteins show different functionality of anti-atherosclerotic properties and embryo toxicity. The Journal of Nutritional Biochemistry. 26(12):1613-21.
Abstract
Among unsaturated fatty acids, epidemiologic studies have demonstrated that ω-6 (linoleic acid) and ω-3 (linolenic acid) fatty acids show different associations with risk of cardiovascular disease (CVD), although its molecular mechanisms remain unclear. To determine why consumption of ω-3 fatty acid is associated with lower risk of CVD, we investigated the biological functions of ω-6 (linoleic acid) and ω-3 (linolenic acid) in reconstituted HDL (rHDL) after encapsulation using human cells and zebrafish embryo. Apolipoprotein A-I (apoA-I) is the principal protein behind the beneficial functions of HDL, which include potent anti-oxidant, anti-inflammatory, and anti-atherosclerotic activities in blood. Several rHDLs were synthesized with apoA-I and different molar ratio of ω-6 or ω-3 fatty acid. Both fatty acids showed similar solubility in rHDL up to a molar ratio of 95:5:1:10 (palmitoyloleoyl phosphatidylcholine:cholesterol:apoA-I:fatty acid). Although both rHDL showed similar structural properties and α-helical contents, ω-6-rHDL showed loss of anti-oxidant ability against LDL oxidation. Uptake of acetylated LDL into macrophages was inhibited by ω-3-rHDL but not ω-6-rHDL, suggesting that ω-6-rHDL has higher pro-atherosclerotic activity. ω-3-rHDL showed more enhanced cholesterol efflux activity with less accumulation of triglyceride in the macrophage. ω-6-rHDL caused more senescence in human dermal fibroblast cells with cytotoxicity, while ω-3-rHDL treatment inhibited the senescence. In zebrafish embryo survivability, ω-3-rHDL-injected embryos showed 86±3% survival, whereas ω-6-rHDL-injected ones showed 72±2% survival as well as an elevated inflammatory response in zebrafish embryos. In conclusion, ω-6-rHDL and ω-3-rHDL show different physiological activities in atherosclerosis, inflammation, and cellular senescence.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping