title: Identification of genes whose expression is altered by obesity throughout the arterial tree.
abstract: We used next-generation RNA sequencing (RNA-Seq) technology on the whole transcriptome to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, we examined transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats. Within the gastrocnemius and soleus muscles, the number of genes differentially expressed with obesity tended to increase with increasing branch order arteriole number (i.e., decreasing size of the artery). This trend was opposite in the diaphragm. We found a total of 15 genes that were consistently upregulated with obesity (MIS18A, CTRB1, FAM151B, FOLR2, PXMP4, OAS1B, SREBF2, KLRA17, SLC25A44, SNX10, SLFN3, MEF2BNB, IRF7, RAD23A, LGALS3BP) and five genes that were consistently downregulated with obesity (C2, GOLGA7, RIN3, PCP4, CYP2E1). A small fraction (∼9%) of the genes affected by obesity was modulated across all arteries examined. In conclusion, the present study identifies a select number of genes (i.e., 20 genes) whose expression is consistently altered throughout the arterial network in response to obesity and provides further insight into the heterogeneous vascular effects of obesity. Although there is no known direct function of the majority of 20 genes related to vascular health, the obesity-associated upregulation of SREBF2, LGALS3BP, IRF7, and FOLR2 across all arteries is suggestive of an unfavorable vascular phenotypic alteration with obesity. These data may serve as an important resource for identifying novel therapeutic targets against obesity-related vascular complications.
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Child Health, University of Missouri, Columbia, Missouri; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; padillaja@missouri.edu.
authors.forename: Jaume
authors.initials: J
authors.lastname: Padilla
authors.affiliation: Kinesiology, University of Georgia, Athens, Georgia;
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Jenkins
authors.affiliation: Biomedical Sciences, University of Missouri, Columbia, Missouri;
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Thorne
authors.affiliation: Biomedical Sciences, Quinnipiac University, Hamden, Connecticut;
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Martin
authors.affiliation: Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri; Research Service-Harry S Truman Memorial VA Medical Center, Columbia, Missouri; Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri;
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rector
authors.affiliation: Health Management and Informatics, University of Missouri, Columbia, Missouri; Statistics, University of Missouri, Columbia, Missouri; MU Informatics Institute, University of Missouri, Columbia, Missouri; and.
authors.forename: J Wade
authors.initials: JW
authors.lastname: Davis
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; Biomedical Sciences, University of Missouri, Columbia, Missouri; Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri.
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology*; D001835:Body Weight; D015536:Down-Regulation / Q000235:genetics; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008297:Male; D009765:Obesity / Q000235:genetics*; D020334:Rats, Inbred OLETF; D015854:Up-Regulation / Q000235:genetics
keywords: OLETF rat model; Type 2 diabetes; gene expression; next-generation sequencing; resistance arteries; vascular dysfunction