Item Details

title

Contrasting Effects of Mediterranean and Western Diets on Vascular, Metabolic, and Brain Health in Socially Dominant and Subordinate Female Cynomolgus Macaques

author

Abusheikha, Aya

abstract

Diet quality and psychosocial stress are two major, modifiable determinants of chronic disease risk. This dissertation explores how long-term dietary habits and social status affect vascular, metabolic, and brain health using a controlled nonhuman primate model. In a 39-month randomized preclinical trial, adult female cynomolgus macaques (Macaca fascicularis) were socially housed to establish social hierarchies, then randomized into either a Western or Mediterranean diets. This study comprehensively assessed behavioral, physiological, and molecular outcomes over time, with a focus on the effects of diet and social status. Compared to the Western cohort, the Mediterranean cohort exhibited with a lower atherosclerosis (intimal area) in the left anterior descending (LAD) coronary artery, and reduced visceral and subcutaneous adiposity. Transcriptomic analyses of key tissues, including iliac and carotid arteries, and visceral adipose tissue (VAT), revealed differential transcriptional profiles in response to diet or social status. The transcriptional differences of these tissues were associated with cerebrospinal fluid (CSF) biomarkers of neurodegeneration. In the iliac artery, diet altered the transcriptional levels of genes associated with endothelial dysfunction, smooth muscle proliferation and migration, angiogenesis, and abnormal extracellular matrix (ECM) dynamics. While in the carotid artery, diet did not induce major effects, but social status altered the transcriptional levels of genes associated with dysregulated vascular tone and smooth muscle contractility, apoptosis, and abnormal ECM dynamics. These findings in demonstrate differential effects of diet composition and social status depending on arterial site. In VAT, diet altered the transcriptional levels of genes associated with fatty acid oxidation, aerobic respiration, RNA processing and protein folding. The transcriptional profiles of iliac and carotid arteries, and VAT associated with mitochondrial respiration, ribosomal activity, inflammation, and lipid metabolism exhibited an association with CSF neurodegenerative biomarkers. These findings highlight the distinct and tissue-specific impacts of long-term diet and social status on vascular and metabolic health, and underscore their relevance to neurodegenerative processes. The observed associations between peripheral tissue transcriptomes and CSF biomarkers suggest that the molecular effects of lifestyle factors extend beyond local tissue environments to potentially influence brain health. This work provides compelling evidence that diet and social stress modulate interconnected pathways across multiple systems, offering novel insights into mechanisms linking lifestyle, chronic disease, and neurodegeneration

subject

Atherosclerosis

Brain Health

Mediterranean Diet

Metabolic Syndrome

Social Status

Western Diet

contributor

Register, Thomas C (advisor)

Zimmerman, Kip D (committee member)

Shively, Carol A (committee member)

Howard, Timothy D (committee member)

Miller, Lance D (committee member)

Hawkins, Greg A (committee member)

date

2025-06-24T08:36:36Z (accessioned)

2025 (issued)

degree

Molecular Genetics & Genomics (discipline)

embargo

2026-06-23 (terms)

2026-06-23 (liftdate)

identifier

http://hdl.handle.net/10339/111038 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation