The goal is to challenge metabolically healthy human subjects with a high-calorie, Western diet for 8 weeks to identify the metabolite(s) responsible for monocyte priming and use redox proteomics, RNAseq and Chipseq to determine the genes and pathways involved in monocyte priming in humans. To reflect some key components of the typical Western intake, the Study Team will compose the diet to be high in saturated fat (15% of total energy intake) and fructose (14% of total energy intake) with excess energy intake that is 25% higher than estimated total energy expenditure. A total of 30 participants, including 15 men and 15 women, will complete a run-in phase where weight stability will be achieved on the control diet. After weight is stabilized during the run-in period, participants will enter the experimental phase of the dietary intervention, where overfeeding will begin with additional calories provided by the key nutrients as noted above. Participants will be monitored throughout the feeding trial. After completion of the 8-week overfeeding period, individuals will be allowed to return to a normal dietary intake. All study participants will be given access to counseling for weight reduction should it be needed following the overfeeding period.
To determine the mechanism of monocyte priming in humans, the study team will conduct a complete feeding trial in normal weight and metabolically healthy human subjects (20-45 years of age) using a western diet (WD), characterized as being high-saturated fat, high-fructose, and high-calorie for 8 weeks.