Genomic and Metabolic Disposition of Non-Obese Type 2 Diabetic Rats to Increased Myocardial Fatty Acid Metabolism
Year: 2013
Type: article
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.
Source: PLoS ONE
Authors: Sriram Devanathan, Samuel T. Nemanich, Attila Kovacs, Nicole Fettig, Robert J. Gropler, Kooresh I. Shoghi
Institution: Washington University in St. Louis
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: National Institutes of Health, Nutrition Obesity Research Center, University of North Carolina, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources
Awards: G151374072, G1820934280, Diabetes Research & Training Center, G2337220457, HIGH RESOLUTION ULTRASOUND SYSTEM FOR CARDIOVASCULAR PHENOTYPING IN MICE, G3397849212, G4025836268, G5128811249, MULTI-TISSUE MULTI-TRACER METABOLIC PHENOTYPING OF DIABETES WITH PRE-CLINICAL PET, G87705910, G9000081704, G9000120519
OpenAlex ID: W2046347883