skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT

Journal Article · · Molecular Imaging
 [1];  [2];  [1];  [1];  [1];  [3];  [4];  [4]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Univ. of California Davis, Sacramento, CA (United States)
  3. Univ. of California, San Francisco, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States); UC Berkeley - UCSF Graduate Program in Bioengineering, Berkeley and San Francisco, CA (United States)

Using longitudinal micro positron emission tomography (microPET)/computed tomography (CT) studies, we quantified changes in myocardial metabolism and perfusion in spontaneously hypertensive rats (SHRs), a model of left ventricular hypertrophy (LVH). Fatty acid and glucose metabolism were quantified in the hearts of SHRs and Wistar-Kyoto (WKY) normotensive rats using long-chain fatty acid analog 18F-fluoro-6-thia heptadecanoic acid (18F-FTHA) and glucose analog 18F-fluorodeoxyglucose (18F-FDG) under normal or fasting conditions. We also used 18F-fluorodihydrorotenol (18F-FDHROL) to investigate perfusion in their hearts without fasting. Rats were imaged at 4 or 5 times over their life cycle. Compartment modeling was used to estimate the rate constants for the radiotracers. Blood samples were obtained and analyzed for glucose and free fatty acid concentrations. SHRs demonstrated no significant difference in 18F-FDHROL wash-in rate constant (P = .1) and distribution volume (P = .1), significantly higher 18F-FDG myocardial influx rate constant (P = 4×10–8), and significantly lower 18F-FTHA myocardial influx rate constant (P = .007) than WKYs during the 2009-2010 study without fasting. SHRs demonstrated a significantly higher 18F-FDHROL wash-in rate constant (P = 5×10–6) and distribution volume (P = 3×10–8), significantly higher 18F-FDG myocardial influx rate constant (P = 3×10–8), and a higher trend of 18F-FTHA myocardial influx rate constant (not significant, P = .1) than WKYs during the 2011–2012 study with fasting. Changes in glucose plasma concentrations were generally negatively correlated with corresponding radiotracer influx rate constant changes. The study indicates a switch from preferred fatty acid metabolism to increased glucose metabolism with hypertrophy. Increased perfusion during the 2011-2012 study may be indicative of increased aerobic metabolism in the SHR model of LVH.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1408473
Journal Information:
Molecular Imaging, Vol. 16; ISSN 1536-0121
Publisher:
SAGECopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

References (39)

Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy journal January 2011
Metabolic Energetics and Genetics in the Heart journal June 2005
Kinetic parameter estimation using a closed-form expression via integration by parts journal September 2012
Targets and probes for non-invasive imaging of β-cells journal December 2016
Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus journal September 2016
Hypertensive left ventricular hypertrophy is associated with abnormal myocardial fatty acid metabolism and myocardial efficiency journal June 2006
Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data journal March 1983
Remodeling of Glucose Metabolism Precedes Pressure Overload-Induced Left Ventricular Hypertrophy: Review of a Hypothesis journal January 2015
Distinct mechanisms for diastolic dysfunction in diabetes mellitus and chronic pressure-overload journal May 2011
Induction of diabetes by Streptozotocin in rats journal September 2007
Relationship Between Carbohydrate and Lipid Metabolism and the Energy Balance of Heart Muscle journal March 1974
Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats journal January 2016
Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress journal March 2015
Myocardial Substrate Metabolism in the Normal and Failing Heart journal July 2005
Imaging of Brown Adipose Tissue: State of the Art journal July 2016
Longitudinal Evaluation of Left Ventricular Substrate Metabolism, Perfusion, and Dysfunction in the Spontaneously Hypertensive Rat Model of Hypertrophy Using Small-Animal PET/CT Imaging journal October 2013
Graphical analysis of PET data applied to reversible and irreversible tracers journal October 2000
Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats journal January 2013
Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy journal July 2002
Molecular distinction between physiological and pathological cardiac hypertrophy: Experimental findings and therapeutic strategies journal October 2010
Mitochondria in cardiac hypertrophy and heart failure journal February 2013
Transition from compensated hypertrophy to systolic heart failure in the spontaneously hypertensive rat: Structure, function, and transcript analysis journal February 2010
Age-related changes of myocardial ATP supply and demand mechanisms journal October 2013
In vivo alterations in cardiac metabolism and function in the spontaneously hypertensive rat heart journal May 2012
Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging journal December 2011
Proteomic adaptation to chronic high intensity swimming training in the rat heart journal March 2008
Cardiac Hypertrophy by Hypertension and Exercise Training Exhibits Different Gene Expression of Enzymes in Energy Metabolism journal January 2003
Defective Fatty Acid Uptake in the Spontaneously Hypertensive Rat Is a Primary Determinant of Altered Glucose Metabolism, Hyperinsulinemia, and Myocardial Hypertrophy journal April 2001
Myocardial Fatty Acid Metabolism: Independent Predictor of Left Ventricular Mass in Hypertensive Heart Disease journal January 2003
Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus journal August 2016
Expression and localization of the AT 1 and AT 2 angiotensin II receptors and α 1A and α 1D adrenergic receptors in aorta of hypertensive and diabetic rats journal January 2017
Metabolism of the human heart journal April 1954
Insights into Brown Adipose Tissue Physiology as Revealed by Imaging Studies journal October 2014
The spontaneously hypertensive rat as a model of the transition from compensated left ventricular hypertrophy to failure journal January 1995
Total-body and myocardial substrate oxidation in congestive heart failure journal February 1994
Gender-Related Effects on Substrate Utilization and Metabolic Adaptation in Hairless Spontaneously Hypertensive Rat journal February 2015
Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity journal April 2015
Old spontaneously hypertensive rats gather together typical features of human chronic left-ventricular dysfunction with preserved ejection fraction journal January 2014
Regional blood flow in normotensive and spontaneously hypertensive rats journal March 1976