Exploring N-3 PUFA Regulation of Lipid Handling Through the Modulation of LPL Activity
This thesis explored the relationship between omega-3 fatty acids (N-3 PUFAs), angiopoietin-like 4 (ANGPTL4), and lipoprotein lipase (LPL) using an in vitro 3T3-L1 adipocyte model. Cells were treated with 100µM alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) for 48 hours. EPA and DHA, but not ALA, upregulated Angptl4 gene expression, and this was associated with the inhibition of LPL activity. PPARγ activity and insulin signaling are known to regulate Angptl4. As such, N-3 PUFA regulation of Angptl4 through PPARγ was further explored with a PPARγ antagonist bisphenol A diglycidyl ether (BADGE); however, it was found that the 48-hour treatment model may not be an optimal time period to explore this relationship. N-3 PUFA regulation of Angptl4 through the modulation of insulin signaling was also explored; however, a lower concentration of insulin in the treatment media may be required to adequately examine this relationship. Collectively, this thesis suggests that N-3 PUFAs differentially regulate Angptl4 expression and LPL activity, though the standard 3T1-L1 culture conditions may need to be adjusted to better delineate the mechanisms of action.