Abstract 13285: Short-term Low-saturated Fat Diet Compared to High-saturated Fat Diet Improves Monocyte Phenotypes in Subjects With Hypertriglyceridemia

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Introduction: Clinical trials suggest that low-saturated fat diet (LSFD) may reduce the risk of atherosclerotic cardiovascular disease (ASCVD) in subjects with hypertriglyceridemia (HTG). Monocytes play crucial roles in atherogenesis. Hypothesis: LSFD vs high-saturated fat diet (HSFD) improves monocyte phenotypes, thereby reducing ASCVD risk, in subjects with HTG. Methods: Subjects with HTG and metabolic syndrome (MetS, n=19) 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) plus a breakfast on day 5, separated by a 4- to 6-week washout period. Blood was drawn on day 1 fasting before the diets and 3 times on day 5 (fasting before the breakfast and 4 and 6 hours postprandial) for measurement of lipid profile and analyses of monocyte phenotypes by flow cytometry and monocyte adhesion by a lab-on-a-chip microfluidic assay. Results: On day 5, LSFD, compared to HSFD, induced lower plasma levels of postprandial total triglyceride and LDL-triglyceride and fasting and postprandial total cholesterol, LDL-cholesterol, and small dense LDL-cholesterol. Compared to HSFD, LSFD reduced fasting and postprandial intracellular lipid accumulation in classical and intermediate monocytes examined by nile red staining and indicated by side scatter value of flow cytometric analysis. LSFD versus HSFD also reduced ex vivo uptake of oxidized LDL by classical monocytes at 4 hours postprandially and by intermediate monocytes in fasting state. Surface levels of molecules involved in monocyte adhesion/migration, including CD11c, CD81, and CCR2, were lower on monocytes with LSFD than with HSFD. Consistently, LSFD compared to HSFD reduced monocyte adhesion to VCAM-1. Intracellular levels of cytokines such as IL-1β, TNFα, and IL-6 in monocytes showed no difference between the two diets. Conclusions: In subjects with HTG and MetS, short-term LSFD compared to HSFD reduces monocyte intracellular lipid accumulation and improves monocyte phenotypes with reductions in monocyte adhesion and oxidized LDL uptake. These findings highlight the importance of diet composition in monocyte phenotypes and possibly atherosclerosis risks in patients with HTG and MetS.

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