High-Fat Feeding Alters Circulating Triglyceride Composition: Roles of FFA Desaturation and ω-3 Fatty Acid...

Hypertriglyceridemia is a risk factor for type 2 diabetes and cardiovascular disease (CVD). Plasma triglycerides (TGs) are a key factor for assessing the risk of diabetes or CVD. However, previous lipidomics studies have demonstrated that not all TG molecules behave the same way. 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 diabetes risk (TGs with lower carbon number [C#] and double-bond number [DB#]), or with decreased risk (TGs with higher C# and DB#). In this study, we examined the effects of high-fat feeding in rats on plasma lipid profiles with special attention to TG profiles. Wistar rats were maintained on either a low-fat (control) or high-fat diet (HFD) for 2 weeks. Plasma samples were obtained before and 2.5 h after a meal (n = 10 each) and subjected to lipidomics analyses. High-fat feeding significantly impacted circulating lipid profiles, with the most significant effects observed on TG profile. The effects of an HFD on individual TG species depended on DB# in their fatty acid chains; an HFD increased TGs with low DB#, associated with increased diabetes risk, but decreased TGs with high DB#, associated with decreased risk. These changes in TGs with an HFD were associated with decreased indices of hepatic stearoyl-CoA desaturase (SCD) activity, assessed from hepatic fatty acid profiles. 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, an HFD selectively depleted ω-3 polyunsaturated fatty acids (PUFAs), contributing to the decreases in TGs with high DB#. Thus, an HFD had profound impacts on circulating TG profiles. Some of these changes were at least partly explained by decreased hepatic SCD activity and depleted ω-3 PUFA.