Date of Completion

9-10-2018

Embargo Period

9-8-2023

Advisors

Christopher Blesso, PhD, Ji-Young Lee, PhD, Maria-Luz Fernandez, PhD

Field of Study

Nutritional Science

Degree

Master of Science

Open Access

Campus Access

Abstract

Background: Cardiovascular disease (CVD) is a leading cause of death globally and is often attributed to atherosclerosis, the accumulation of cholesterol-rich plaques in arteries. Many cholesterol-lowering drugs have undesirable side effects. Therefore, finding safe dietary bioactives that can have similar effects to these pharmaceuticals is important. Our preliminary research demonstrated that dietary bovine milk sphingomyelin (SM), a polar lipid (PL) component of milk fat globule membranes (MFGM), reduces both blood and liver lipids, and inflammatory markers in mice fed a high-fat diet (HFD). As purified SM is expensive, a nutritionally-rich source of SM and other PL, in the form of butter serum, was investigated in this study.

Methods: Male LDLr-/-mice (N = 45) were fed one of three anhydrous milk fat diets for 14 weeks: HFD control (CTL; 45% kcal from fat, 0.22% cholesterol, n= 15), HFD diet supplemented with 1% milk PLs (1% MPL; n= 15), or HFD supplemented with 2% milk PLs (2% MPL; n= 15). Serum lipid and inflammatory protein levels were attained. Aortas were analyzed for lesions.

Results: Serum cholesterol was significantly lower by 51% with 2% MPL compared to CTL. Fast protein liquid chromatography (FPLC) of serum showed a dose-dependent reduction in cholesterol found in VLDL and LDL fractions in MPL groups compared to CTL. Serum MCP-1 concentrations were lower by 56% in the 2% MPL group compared to CTL; however, no significant changes in TNF-α, IL-1β, or SAA were observed. En faceanalysis of thoracic aorta atherosclerosis showed a significant 55% decrease in total Oil Red O (ORO) neutral lipid lesion size in the 2% MPL group when compared to CTL. Aortic %ORO lesion area was positively correlated with serum cholesterol (r = 0.384, p< 0.01). The mRNA expression of MCP-1 was lower in the descending aorta of 2% MPL group, while IL-1β mRNA was elevated in the 1% MPL group compared to CTL.

Conclusion: These results suggest that milk PLs play a role in modifying the response to a Western-type diet rich in saturated fat and cholesterol. Animals fed the 2% MPL had a strong lowering in atherosclerosis development and atherogenic lipoprotein cholesterol compared to controls in LDLr-/-mice; however, further research is needed to clarify its effect on inflammatory pathways.

Major Advisor

Christopher Blesso

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