Monocyte Priming When Consuming a Western Diet

Mechanism of Monocyte Priming in Humans - a Feeding Trial

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.

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. Participants will complete a run-in phase where weight stability will be achieved on the control diet. No outcome measures will be collected from the run-in phase. 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.

Inclusion Criteria:

• Age 20-45
• Planning to be available for the entire study period
• Able to speak and read English
• Normal weight (body mass index 18.5-24.9 kg/m2)
• Able to eat the prescribed diet
• Non-smoker

Exclusion Criteria:

• Excessive alcohol consumption
• History of chronic cardiometabolic disease or major risk factor, including diabetes, hypertension, hyperlipidemia, heart disease
• History of prior surgical procedure for weight control or liposuction
• Use of weight loss medications in previous 6 months
• Recent self-reported weight change
• Severe pulmonary disease requiring supplemental oxygen
• Abnormal renal or liver function
• History of non-skin cancer in the past 5 years
• Regular use of medications (prescribed or over-the-counter) that affect blood pressure, lipids, glucose, inflammation, or body weight
• Works night shifts
• Exercise per week > 420 minutes total for moderate activity or > 210 minutes for vigorous activity
• Any medical or behavioral indication that would make participation unsafe based on the judgement of the study physician
• Pregnant or lactating women
• Known or discovered intolerances, allergies or difficulty consuming any of the foods included in the study diets