Clinical trial NCT05235464: High Protein Diet and Atherosclerosis
Official title: Dissecting the Impact of Dietary Protein on Macrophage MTOR Signaling and Atherosclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atherosclerosis
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
First posted: 2022-02-11
Enrollment: 24
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized cross-over study
Primary purpose: OTHER

Brief summary: Atherosclerosis is the underlying cause of the majority of cardiovascular diseases, including myocardial infarction and strokes, and results in tremendous morbidity and mortality. A Western-type diet is a major risk factor for atherosclerosis because of the high saturated fat, cholesterol, and refined carbohydrate contents. Dietary strategies to reduce cardiovascular disease burden therefore focus on restriction of saturated fat, cholesterol, and refined carbohydrates whereas "lean" protein intake is recommended and has become popular. However, results from studies conducted in animal models suggest high dietary protein intake is also atherogenic. The investigators' extensive preliminary data in animal models show that dietary protein increases atherosclerotic plaque formation and size and promotes necrotic core formation, a characteristic of rupture-prone plaques. The goal of the current proposal is to provide deeper insights into the relationship between protein intake and the pathogenesis of atherosclerosis by studying the mechanisms involved in protein-mediated atherogenesis and formation of necrotic plaques. The overarching hypothesis is that high protein intake drives atherosclerosis via leucine-mediated mTORC1 signaling in macrophages, which inhibits macrophage mitophagy and aggrephagy and stimulates macrophage proliferation. Furthermore, the investigators hypothesize that proteins from animal sources are more atherogenic than proteins from plant sources, because animal proteins contain more leucine than plant proteins. The investigators will test these hypotheses by using a sophisticated array of experimental strategies, including assays in primary macrophages and human monocyte-derived macrophages and genetically engineered mouse models. In addition, they will begin to translate the results obtained in vitro and in animals to people, and explore approaches to pharmacologically target the pro-atherogenic pathways as novel cardiovascular therapeutics. This proposal represents a paradigm shift in how a Western-type diet affects vascular health which has important implications since many adults in Western societies consume excess protein and dietary protein is heavily marketed for its presumed beneficial health effects.


Eligibility criteria: Inclusion Criteria:

* \>=45 and \<=75 years of age
* body mass index \>=25.0 and \<40.0 kg/m2

Exclusion Criteria:

* \<45 and \>75 years of age
* body mass index \<25.0 or \>39.9 kg/m2
* plasma triglyceride \<125 mg/dl
* history of or current significant organ system dysfunction
* allergies or intolerances to meal ingredients
* use of medications or dietary supplements that could confound the study outcomes
* engaged in regular structured exercise \>150 min per week
* alcohol use disorder
* premenopausal women
* persons who smoke
* prisoners
* inability to grant voluntary informed consent

Primary outcomes:
measure: Monocyte p-S6 content
timeFrame: change from at 1 hour before meal intake and 3 hours after the meal
Secondary outcomes:
Other outcomes:
Locations:
city: Columbia
country: United States
facility: University of Missouri School of Medicine
state: Missouri
Study officials:
affiliation: University of Missouri-Columbia
name: Bettina Mittendorfer
role: PRINCIPAL_INVESTIGATOR
References: