Monocyte Priming When Consuming a Western Diet
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Experimental diet The experimental diet will provide 15% of calories from saturated fat and 14% of calories from fructose with a goal of providing 1.25x total energy needs |
Other: Experimental diet
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.
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Outcome Measures
Primary Outcome Measures
- Measurement of Mitogen-activated protein kinase phosphate 1 (MKP-1) activity [change in at the endpoint of week 8]
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
Secondary Outcome Measures
- Measurement of Monocyte protein S-glutathionylation [change in at the endpoint of week 8]
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.
Other Outcome Measures
- Ribonucleic acid (RNA) analysis [change in at the endpoint of week 8]
Determine the genes and pathways involved in monocyte priming in humans. Quantify mRNA expression of all transcripts in expressed monocytes
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 20-45
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Planning to be available for the entire study period
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Able to speak and read English
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Normal weight (body mass index 18.5-24.9 kg/m2)
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Able to eat the prescribed diet
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Non-smoker
Exclusion Criteria:
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Excessive alcohol consumption
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History of chronic cardiometabolic disease or major risk factor, including diabetes, hypertension, hyperlipidemia, heart disease
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History of prior surgical procedure for weight control or liposuction
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Use of weight loss medications in previous 6 months
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Recent self-reported weight change
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Severe pulmonary disease requiring supplemental oxygen
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Abnormal renal or liver function
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History of non-skin cancer in the past 5 years
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Regular use of medications (prescribed or over-the-counter) that affect blood pressure, lipids, glucose, inflammation, or body weight
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Works night shifts
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Exercise per week > 420 minutes total for moderate activity or > 210 minutes for vigorous activity
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Any medical or behavioral indication that would make participation unsafe based on the judgement of the study physician
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Pregnant or lactating women
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Known or discovered intolerances, allergies or difficulty consuming any of the foods included in the study diets
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
Sponsors and Collaborators
- Wake Forest University Health Sciences
- National Institutes of Health (NIH)
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Jamy Ard, MD, Wake Forest University Health Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00083476
- R01HL153120