Monocytes are a heterogeneous population of circulating blood cells that contribute to tissue integrity as well as to innate and adaptive immune defense. There are three well-characterized subsets based on their relative expression of surface antigens, cluster of differentiation 14 (CD14) and cluster of differentiation 16 (CD16). Monocytes originate from myeloid precursors in the bone marrow and enter the circulation as classical monocytes (CLMs). CLMs represent a transient cell population with a diverse differentiation potential. CLMs comprise 80-90% of the circulating blood monocyte pool and remain in circulation for approximately one day before either migrating into tissue to repopulate the tissue resident macrophage population or maturing into non-classical monocytes (NCMs). NCMs comprise only 5-10% of the circulating blood monocyte pool but have a much longer circulating lifespan of approximately 7 days. NCMs exhibit conflicting functions as anti-inflammatory caretakers of vascular tissue and as contributors to the pathogenesis of disease.~Metabolic responses to food consumption influence the risk of cardiometabolic disease. Postprandial glycemia and lipemia modulate vascular health by altering endothelial function and inducing oxidative stress, inflammation, and apoptosis. Consumption of a single high-fat meal increases circulating interleukin 6 (IL-6), enhances expression of monocyte adhesion molecules, reduces flow-mediated dilation, and increases markers of oxidative stress in human subjects. Although NCMs are described as vascular housekeepers with distinct motility and crawling patterns allowing them to actively surveil endothelium and scavenge luminal debris, their role in the postprandial state is currently unknown.~To better understand the function of postprandial NCMs following consumption of a single high-fat mixed macronutrient challenge meal, the investigators propose a study following a crossover design in which participants will consume one of two isocaloric high-fat challenge meals spaced two-weeks apart, a high-saturated fat mixed macronutrient challenge meal or a high-monounsaturated fat mixed macronutrient challenge meal. Blood at fasting and at six hours postprandial will be collected and the proportion of NCMs and their integrin expression will be analyzed by flow cytometry while changes in global gene expression will be measured by RNA-sequencing.
The purpose of this research is to determine the role of a type of immune cell in blood, called a non-classical monocytes (NCMs), following consumption of a high-fat meal. Previous studies have found that monocytes are important for blood vessel health. In this study, two different high-fat meals will be used to study the effect of different types of dietary fat on postprandial NCMs. The investigators will characterize NCMs in both fasting conditions and following consumption of two different high-fat meals, and will evaluate whether the type of fat in a meal affects NCMs in blood.