Cardiovascular diseases are the leading causes of death globally, placing an enormous burden on individuals as well as medical and social programs worldwide. Although omega-3 polyunsaturated fatty acids (n3-PUFA) are well recognized for their triglyceride-lowering properties, the vast majority of people worldwide consume insufficient levels to gain their full benefit. The goal of this project is to examine the interactions between n3-PUFA and genetic variants, and their association with blood triglyceride levels. Genetic variants in angiopoetin-like (ANGPTL) genes have been previously associated with circulating triglyceride levels and cardiovascular disease risk; however, the ability of these associations to be modified by n3-PUFA is unknown. Therefore, the proposed project will explore how common variants in and near ANGPTL genes are associated with blood triglycerides and other cardiometabolic risk factors, and whether these associations are modified according to an individual’s n3-PUFA levels. N3-PUFA are known to have triglyceride-lowering effects, which is generally attributed to their ability to suppress hepatic de novo lipogenesis. However, emerging evidence suggests that n3-PUFA may also regulate ANGPTL proteins, which consequently influences lipoprotein lipase (LPL) activity. LPL is responsible for the break down of blood triglycerides, which releases fatty acids for uptake into tissues such as adipose. The knowledge generated from this work has the potential to uncover a novel role for n3-PUFA that will provide additional evidence to support their hypotriglyceridemic properties and their potential cardiovascular benefits. Moreover, this insight may help guide personalized dietary strategies to reduce cardiovascular disease burden.
