Abstract 11296: Short-Term Low-Saturated Fat Diet Compared to High-Saturated Fat Diet in Patients with Hypertriglyceridemia: Lipids and Lipoproteins Associated with Monocyte Phenotypic Changes

Abstract

Background: Monocyte phenotypic changes play a pivotal role in atherogenesis and can be induced by plasma lipids. We analyzed associations of monocyte phenotypes with lipid profiles and the potential of predicting monocyte phenotypes by lipid variables in subjects with hypertriglyceridemia (HTG) after short-term intake of low-saturated fat diet (LSFD) and high-saturated fat diet (HSFD). Method: Subjects with HTG (n=19, 10 men and 9 women, aged 53.9±13.7 years) received isocaloric LSFD (~25% of calories from fat, 5% from saturated fat) and HSFD (~52% of calories from fat, 25% from saturated fat) in randomized order for 4 days (days 1-4) and a test meal on day 5, separated by a 4- to 6-week washout period. Blood was taken on day 1 fasting before the diets and on day 5 fasting and 4 and 6 hours after the test meal to examine lipoprotein profile by enzymatic assay, fatty acids by nuclear magnetic resonance spectroscopy, and monocyte phenotypes by flow cytometry. Least absolute shrinkage and selection operator (LASSO) regression models were built to identify influential lipid variables for key monocyte markers that responded differently to the two diets. Results: LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride (TG), VLDL-TG, and LDL-TG and fasting and postprandial total cholesterol and LDL-cholesterol and altered fatty acid composition, with reduced saturated fatty acids (SFAs) but increased polyunsaturated fatty acids (PUFAs). Compared to HSFD, LSFD reduced monocyte lipid accumulation and levels of several surface markers involved in monocyte adhesion and migration including CD11c, a β2 integrin, on intermediate monocytes. Using the LASSO regression models, we identified that total cholesterol, LDL-TG, and apoB were positively correlated and n-3 PUFAs negatively correlated with lipid accumulation in intermediate monocytes and that total TG, LDL-TG, and apoCIII were positively correlated with CD11c levels on intermediate monocytes. Conclusions: In subjects with HTG, short-term LSFD compared to HSFD improves lipid profiles and monocyte phenotypes. We also identified specific plasma lipid parameters that may be reliable predictors for and contribute to specific monocyte phenotypic changes in HTG.