Monocyte Priming When Consuming a Western Diet

Wake Forest University Health Sciences8 enrolled

Overview

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. 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Heart Diseases

Interventions

Experimental dietOTHER

Participants that successfully complete the run-in phase will participate in the experimental diet for 8 weeks of feeding. The Participants' adherence will be monitored using direct observation, written daily food diaries, and food waste inventory (i.e., participants are trained to estimate portion of uneaten foods). Participants will be asked to eat one meal onsite 2-3 weekdays (e.g., Monday, Wednesday, and Friday), at which time they will receive meals and snacks for the remainder of that day and enough until the next scheduled visit.

Eligibility

Sex: ALLMin age: 20 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Outcomes

Primary Outcomes

Measurement of Mitogen-activated protein kinase phosphate 1 (MKP-1) activity

Analyze plasma from all subjects for their plasma lipid composition using an unbiased lipidomics approach in order to identify the lipid species responsible for monocyte priming

Time frame: change in at the endpoint of week 8

Secondary Outcomes

Measurement of Monocyte protein S-glutathionylation

To identify which proteins alter their S-glutathionylation status (and possibly their expression levels) in response to HCD-induced monocyte priming, and which signaling pathways are altered in these cells. Isolate S-glutathionylated proteins from all samples and subject them to redox proteomics approach to identify S-glutathionylated proteins and to determine the extent and directionality of modifications on their cysteine residues.

Time frame: change in at the endpoint of week 8

Data from ClinicalTrials.gov

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