Abstract 276: Postprandial Effects on Monocyte Phenotype in Obese Humans With Metabolic Syndrome
Monocytes are heterogeneous with 3 subsets in humans, identified by CD14 and CD16 levels and differing in numerous other markers. Under certain stimuli, monocytes undergo phenotypic changes, with accelerated trafficking into tissues, which play crucial roles in inflammation including atherogenesis. We used multicolor flow cytometry to examine postprandial effects of a high-fat meal, containing 910 kcal (53% from fat, 23% from saturated fat) and 535 mg cholesterol, on monocyte phenotype in 11 obese subjects with metabolic syndrome (MS) (BMI: 34.8 ± 2.2 kg/m2; fasting triglyceride [TG]: 217 ± 42 mg/dl) and 11 gender- and age-matched lean controls (BMI: 24.0 ± 0.7 kg/m2; fasting TG: 89 ± 10 mg/dl, P<0.01 vs obese group). Blood was taken after an overnight fast (T0) and at 3 (T3) and 5 (T5) hours after high-fat meal. At T0, obese subjects had higher counts of CD14dim/CD16+ nonclassical monocytes (ncM), but not CD14+/CD16- classical (cM) and CD14+/CD16+ intermediate monocytes (iM), than leans. Mean fluorescent intensity (MFI) of CD11c, CCR5 and HLA-DR, and percentages of TNFα+ and IL-1β+ cells were higher on/in iM and ncM than on/in cM (P<0.05) in each individual at T0, supporting inflammatory phenotype of iM and ncM. Compared to lean, obese subjects had higher levels of CD11c on iM and cM, CX3CR1 on iM and CCR5 and TNFα on/in cM and also higher proportion of Nile-red+ lipid-laden foamy monocytes at T0 (P<0.05), which correlated positively with fasting TG levels (P=0.02, r=0.53). After high-fat meal, both obese and lean groups had significant increases in TG levels (TG incremental area under the curve: 344 ± 52 in obese versus 225 ± 28 in leans, P=0.05). The proportions of foamy monocytes were significantly higher at T3 than T0 (P<0.05) in lean subjects and tended to be higher at T3 and T5 than T0 in obese subjects. Obese but not lean subjects had significant increases in CD11c MFI and percentages of IL-1β+ and TNFα+ cells in ncM at T3 compared to T0. In summary, in both obese and lean groups, iM and ncM had proinflammatory phenotype. Compared to leans, obese subjects with MS had increased lipid accumulation and enhanced inflammatory phenotype in monocyte subsets at baseline and showed further increases in inflammatory markers, particularly in ncM, after a high-fat meal.
Author Disclosures: H. Wu: None. I. Khan: None. Y. Pokharel: None. R. Dadu: None. D. Lewis: None. R. Hoogeveen: None. C. Ballantyne: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.