Ignite Creation Date:
2024-05-06 @ 1:08 PM
Last Modification Date:
2024-10-26 @ 1:09 PM
Study NCT ID:
NCT03946774
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-01-31
First Post:
2019-03-12
Brief Title:
Dietary Protein and MonocyteMacrophage Mammalian Target of Rapamycin mTOR Signaling
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
Acute Effects of Dietary Protein on MonocyteMacrophage mTOR Signaling and Downstream Sequela
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
mTOR
Brief Summary:
High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss It is controversial if these diets are associated with an increased risk of cardiovascular disease
The investigators propose to administer high and low protein shakes to participants and measure effects on circulating monocytes immune cells critical to the development of atherosclerosis and cardiovascular disease In order to study circulating monocytes blood will be collected from the study participants just prior to drinking the shake and then 1 and 4 hours after drinking the shake
In order to assess functional effects on monocytes investigators will perform a series of assays comparing the results between individuals who drank high protein vs low protein shakes
The investigators propose to administer high and low protein shakes to participants and measure effects on circulating monocytes immune cells critical to the development of atherosclerosis and cardiovascular disease In order to study circulating monocytes blood will be collected from the study participants just prior to drinking the shake and then 1 and 4 hours after drinking the shake
In order to assess functional effects on monocytes investigators will perform a series of assays comparing the results between individuals who drank high protein vs low protein shakes
Detailed Description:
Cardiovascular disease remains the leading cause of death globally with obesity as of one of the dominant modifiable risk factors Obesity is also a precursor to several other cardiovascular risk factors including hypertension hyperlipidemia and diabetes Almost all weight loss efforts utilize dietary modification with high proteinlow carbohydrate diets serving as one of the most popular approaches Despite the metabolic benefits of high dietary protein recent studies have raised a concerning association with increased risk of atherosclerosis and cardiovascular disease Although this remains controversial there is some animal data showing evidence of dietary proteins proatherogenic role These data are correlative and no mechanistic studies have been undertaken
The downstream events after protein ingestion involve digestion of the protein into amino acids increases in blood amino acids and distribution to target tissues Mouse models have definitively shown that circulating monocytes and macrophages of arterial blood vessels are particularly sensitive to this amino acid load with robust activation of the mTOR mammalian target of rapamycin signaling pathway This in turn leads to inhibition of essential degradative processes of the macrophage such as autophagy and promotes release of pro-inflammatory cytokines Thus macrophage function in vascular beds becomes pathogenic leading to atherogenesis and cardiovascular disease
The translation of these mechanistic studies in animal models to human is the next obvious step in this research However no studies have elucidated the mechanisms of monocyte activation and function following administration of high dietary protein in humans The investigators propose a pilot study to bridge an important gap in translational research which will elucidate the mechanisms by which dietary protein affects human monocyte function and the risk of atherosclerotic plaque formation Specifically the investigators will evaluate the acute activation of mTOR signaling and downstream sequelae in circulating monocytes following the administration of protein shakes This study will address the hypothesis that humans exposed to high dietary protein will have significantly higher post-prandial monocyte mTOR activation with concomitant development of impaired degradative capacity and a proinflammatory state
An understanding of these mechanisms has broad implications in the evaluation and future therapeutic interventions of cardiovascular disease
In addition this can provide a valuable clinical tool for health care providers in educating patients on dietary changes to ameliorate cardiovascular risk
The downstream events after protein ingestion involve digestion of the protein into amino acids increases in blood amino acids and distribution to target tissues Mouse models have definitively shown that circulating monocytes and macrophages of arterial blood vessels are particularly sensitive to this amino acid load with robust activation of the mTOR mammalian target of rapamycin signaling pathway This in turn leads to inhibition of essential degradative processes of the macrophage such as autophagy and promotes release of pro-inflammatory cytokines Thus macrophage function in vascular beds becomes pathogenic leading to atherogenesis and cardiovascular disease
The translation of these mechanistic studies in animal models to human is the next obvious step in this research However no studies have elucidated the mechanisms of monocyte activation and function following administration of high dietary protein in humans The investigators propose a pilot study to bridge an important gap in translational research which will elucidate the mechanisms by which dietary protein affects human monocyte function and the risk of atherosclerotic plaque formation Specifically the investigators will evaluate the acute activation of mTOR signaling and downstream sequelae in circulating monocytes following the administration of protein shakes This study will address the hypothesis that humans exposed to high dietary protein will have significantly higher post-prandial monocyte mTOR activation with concomitant development of impaired degradative capacity and a proinflammatory state
An understanding of these mechanisms has broad implications in the evaluation and future therapeutic interventions of cardiovascular disease
In addition this can provide a valuable clinical tool for health care providers in educating patients on dietary changes to ameliorate cardiovascular risk
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None