Short-term high fat diet alters genes associated with metabolic and vascular dysfunction during adolescence in rats: a pilot study

PeerJ

article

Alex E. Mohr¹  Rebecca A. Reiss²  Monique Beaudet²  Johnny Sena³  Jay S. Naik⁴  Benjimen R. Walker⁴  Karen L. Sweazea⁵ 

[1] College of Health Solutions, Arizona State University;Biology Department, New Mexico Institute of Mining and Technology;National Center for Genome Resources;The Department of Cell Biology and Physiology, University of New Mexico;College of Health Solutions & School of Life Sciences, Arizona State University

关键词: High fat diet;    Aorta;    Cardiovascular;    Gene;    RNA;    Metabolic syndrome;   

DOI  :  10.7717/peerj.11714

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background Diet-induced metabolic dysfunction precedes multiple disease states including diabetes, heart disease, and vascular dysfunction. The critical role of the vasculature in disease progression is established, yet the details of how gene expression changes in early cardiovascular disease remain an enigma. The objective of the current pilot project was to evaluate whether a quantitative assessment of gene expression within the aorta of six-week old healthy male Sprague-Dawley rats compared to those exhibiting symptoms of metabolic dysfunction could reveal potential mediators of vascular dysfunction. Methods RNA was extracted from the aorta of eight rats from a larger experiment; four animals fed a high-fat diet (HFD) known to induce symptoms of metabolic dysfunction (hypertension, increased adiposity, fasting hyperglycemia) and four age-matched healthy animals fed a standard chow diet (CHOW). The bioinformatic workflow included Gene Ontology (GO) biological process enrichment and network analyses. Results The resulting network contained genes relevant to physiological processes including fat and protein metabolism, oxygen transport, hormone regulation, vascular regulation, thermoregulation, and circadian rhythm. The majority of differentially regulated genes were downregulated, including several associated with circadian clock function. In contrast, leptin and 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) were notably upregulated. Leptin is involved in several major energy balance signaling pathways and Hmgcs2 is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis. Conclusion Together, these data describe changes in gene expression within the aortic wall of HFD rats with early metabolic dysfunction and highlight potential pathways and signaling intermediates that may impact the development of early vascular dysfunction.

【 授权许可】

CC BY