Faculty Collaboration Database

Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism. PLoS One 2013;8(10):e78477

Date

11/10/2013

Pubmed ID

24205240

Pubmed Central ID

PMC3804536

DOI

10.1371/journal.pone.0078477

Scopus ID

2-s2.0-84886911139 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM). While numerous reports have demonstrated increased myocardial fatty acid (FA) utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK) rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET) to estimate myocardial blood flow (MBF) and myocardial FA metabolism. Echocardiograms (ECHOs) were performed to assess cardiac function. Levels of triglycerides (TG) and non-esterified fatty acids (NEFA) were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR) arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI) and decrease in peak early diastolic mitral annular velocity (E') compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

Author List

Devanathan S, Nemanich ST, Kovacs A, Fettig N, Gropler RJ, Shoghi KI

Author

Sam Nemanich Ph.D. Assistant Professor in the Occupational Therapy department at Marquette University

MESH terms used to index this publication - Major topics in bold

Animals
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 2
Fatty Acids, Nonesterified
Genomics
Heart
Heart Ventricles
Lipid Metabolism
Male
Myocardium
Obesity
Rats, Wistar
Regional Blood Flow
Transcriptome
Triglycerides