516-P: High-Fat Feeding Alters Circulating Triglyceride Profile by Decreasing SCD Activity and Depleting n-3 Fatty Acids

Introduction and Objective: Hypertriglyceridemia is a risk factor for type 2 diabetes and cardiovascular disease (CVD), and plasma triglyceride (TG) is considered as a major component in the assessment of diabetes or CVD risk. However, previous lipidomics studies demonstrated that not all TG molecules behave similarly, and that individual TGs with different fatty acid compositions are regulated differentially under various conditions. In addition, distinct groups of TGs were identified to be associated with increased (TGs with lower carbon number [C#] and double-bond number [DB#]) or decreased (TGs with higher C# and DB#) diabetes risk. In the present study, we examined the effects of high fat feeding in rats on plasma lipid profiles with special attention to TG profiles.

Methods: Wistar rats were maintained on a low-fat (control) or high-fat (HFD) diet for 2 weeks, and plasma samples were obtained before and 2.5 h after a meal (n = 10 each) and subjected to a lipidomics analysis.

Results: High fat feeding had significant impacts on circulating lipid profiles with most significant effects observed on TG profile. The effects of HFD on individual TG species depended on DB# in their fatty acid chains; HFD increased TGs with low DB#, known to be associated with increased diabetes risk, but decreased TGs with high DB#, known to be associated with decreased diabetes risk. These changes in TGs with HFD were associated with decreased hepatic stearoyl-CoA desaturase (SCD) activity, assessed from hepatic fatty acid profile. Decreased SCD activity would reduce the conversion of saturated to monounsaturated fatty acids, contributing to the increases in saturated TGs or TGs with low DB#. In addition, HFD selectively depleted n-3 polyunsaturated fatty acids (PUFAs), contributing to the decreases in TGs with high DB#.

Conclusion: HFD had profound impacts on circulating TG profile, and some of these changes are explained, at least in part, by decreased SCD activity and depleted n-3 PUFA.