NDLI: Linoleic Acid Suppresses Cholesterol Efflux and ATP-Binding Cassette Transporters in Murine Bone Marrow-Derived Macrophages

Content Provider	Springer Nature Link
Author	Sparta, Nicole L. Lamon Fava, Stefania Matthan, Nirupa R. Obin, Martin S. Greenberg, Andrew S. Lichtenstein, Alice H.
Copyright Year	2014
Abstract	Individuals with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease (CVD), possibly associated with elevated plasma free fatty acid concentrations. Paradoxically, evidence suggests that unsaturated, compared to saturated fatty acids, suppress macrophage cholesterol efflux, favoring cholesterol accumulation in the artery wall. Murine bone marrow-derived macrophages (BMDM) were used to further explore the relationship between saturated and unsaturated fatty acids, and cholesterol efflux mediated by ATP-binding cassette transporters (ABCA1 and ABCG1) through transcription factors liver-x-receptor-alpha (LXR-α) and sterol receptor element binding protein (SREBP)-1. BMDM isolated from C57BL/6 mice were exposed to 100 μM linoleic acid (18:2) or palmitic acid (16:0) for 16 h, and 25 μg/mL oxidized low density lipoprotein for an additional 24 h. ABCA1 and ABCG1 mRNA expression was suppressed to a greater extent by 18:2 (60 % and 54 %, respectively) than 16:0 (30 % and 29 %, respectively) relative to the control (all p < 0.01). 18:2 decreased ABCA1 protein levels by 94 % and high density lipoprotein (HDL) mediated cholesterol efflux by 53 % (both p < 0.05), and had no significant effect on ABCG1, LXR-α or SREBP-1 protein levels. 16:0 had no effect on ABCA1, ABCG1, LXR-α or SREBP-1 protein expression or HDL-mediated cholesterol efflux. These results suggest that 18:2, relative to 16:0, attenuated macrophage HDL-mediated cholesterol efflux through down regulation of ABCA1 mRNA and protein levels but not through changes in LXR-α or SREBP-1 expression. The effect of 18:2 relative to 16:0 on macrophages cholesterol homeostasis may exacerbate the predisposition of individuals with T2DM to increased CVD risk.
Starting Page	415
Ending Page	422
Page Count	8
File Format	PDF
ISSN	00244201
Journal	Lipids
Volume Number	49
Issue Number	5
e-ISSN	15589307
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-03-05
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Bone marrow-derived macrophages Cholesterol efflux ATP-binding cassette transporters Sterol regulatory element binding protein Atherosclerosis Unsaturated fatty acids Lipidology Neurochemistry Medical Biochemistry Nutrition Medicinal Chemistry Microbial Genetics and Genomics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Organic Chemistry Biochemistry

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