Item Details

abstract

Cardiovascular disease (CVD) is the leading cause of death in the United States and Westernized countries. Atherosclerosis, the primary cause of CVD, is characterized by the accumulation of cholesterol-loaded macrophages in the artery wall, resulting in a chronic inflammatory response. Consumption of fish oil (FO) and n-3 polyunsaturated fatty acid (PUFA) supplements has been shown to be cardioprotective and result in several health benefits, including reduced plasma triglyceride (TG) concentration, inflammation, endothelial cell activation, and atherosclerosis. FO contains eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), which are credited for its cardioprotective properties. Despite the documented benefits, FO and n-3 PUFAs are poorly consumed in the Western diet. Furthermore, approximately 90% of the Western diet's n-3 PUFA source is alpha-linolenic acid (ALA, 18:3 n-3), derived from vegetable oils. ALA is poorly converted to EPA and DHA in humans due to the inefficiency of the δ-6 desaturase catalyzed step of fatty acid elongation and desaturation. Echium oil (EO), derived from Echium plantagineum seeds, is enriched (~12%) with stearidonic acid (SDA; 18:4 n-3), the immediate product of ALA δ-6 desaturation, and has been shown to significantly lower plasma TGs in human hypertriglyceridemic subjects and, therefore, may serve as a botanical alternative to FO. This dissertation describes the effect of EO on the development of atherosclerosis and the mechanisms mediating its hypotriglyceridemic effects using male apolipoprotein B100-only low density lipoprotein receptor knockout (apoB100-only LDLrKO) mice, a mildly hypertriglyceridemic model of atherosclerosis with significant plasma TG reduction in response to FO and EO feeding. We show that compared to mice fed palm oil (PO), a diet rich in saturated fat, EO feeding results in significant reductions of aortic cholesterol and aortic surface lesion area, findings that were similar to FO-fed mice. Intravenous injection of detergent to block lipolysis showed that FO-fed mice had decreased plasma TG accumulation compared to EO-fed mice. Surprisingly, hepatic TG content in both the PO- and EO-fed mice was significantly higher than that of FO-fed mice, indicating that EO does not protect against hepatic steatosis in this mouse model. Furthermore, very low density lipoprotein (VLDL) from EO-fed mice incubated with purified lipoprotein lipase (LPL) is significantly more susceptible to hydrolysis than PO-VLDL, and VLDL compositional analysis suggests that EO-VLDL is smaller than PO-VLDL. These results suggest that EO and FO do not reduce plasma TG concentrations by parallel mechanisms. Whereas FO exerts its hypotriglyceridemic effect primarily by decreasing hepatic TG synthesis and secretion, we found that EO reduces plasma TG primarily by increased intravascular TG lipolysis. In summary, EO feeding is cardioprotective and hypotriglyceridemic due to increased intravascular TG lipolysis and may serve as a botanical alternative for FO.

subject

atherosclerosis

Echium oil

fish oil

n-3 fatty acids

polyunsaturated fatty acids

triglyceride

contributor

Forrest, Lolita Marie (author)

Parks, John S. (committee chair)

Rudel, Lawrence L. (committee member)

Edwards, Iris (committee member)

Mishra, Nilamadhab (committee member)

Seeds, Michael (committee member)

date

2011-07-14T20:35:49Z (accessioned)

2012-07-14T08:30:19Z (available)

2011 (issued)

degree

Molecular Medicine and Translational Science (discipline)

embargo

2012-07-14 (terms)

identifier

http://hdl.handle.net/10339/33464 (uri)

language

en (iso)

publisher

Wake Forest University

title

INVESTIGATION OF THE CARDIOPROTECTIVE AND HYPOTRIGLYCERIDEMIC POTENTIAL OF ECHIUM OIL AS A BOTANICAL SOURCE OF LONG CHAIN N-3 FATTY ACIDS

type

Dissertation