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

Abstract

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 influxmore » 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.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [3];  [4];  [4]
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  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)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1408473
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Molecular Imaging
Additional Journal Information:
Journal Volume: 16; Journal ID: ISSN 1536-0121
Publisher:
SAGE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; animal models of disease; quantitation in molecular imaging; cardiovascular; animal pet; cardiac imaging; molecular modeling

Citation Formats

Huber, Jennifer S., Hernandez, Andrew M., Janabi, Mustafa, O’Neil, James P., Brennan, Kathleen M., Murphy, Stephanie T., Seo, Youngho, and Gullberg, Grant T. Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT. United States: N. p., 2017. Web. doi:10.1177/1536012117724558.
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Huber, Jennifer S., Hernandez, Andrew M., Janabi, Mustafa, O’Neil, James P., Brennan, Kathleen M., Murphy, Stephanie T., Seo, Youngho, & Gullberg, Grant T. Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT. United States. https://doi.org/10.1177/1536012117724558
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Huber, Jennifer S., Hernandez, Andrew M., Janabi, Mustafa, O’Neil, James P., Brennan, Kathleen M., Murphy, Stephanie T., Seo, Youngho, and Gullberg, Grant T. Wed . "Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT". United States. https://doi.org/10.1177/1536012117724558. https://www.osti.gov/servlets/purl/1408473.
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@article{osti_1408473,
title = {Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT},
author = {Huber, Jennifer S. and Hernandez, Andrew M. and Janabi, Mustafa and O’Neil, James P. and Brennan, Kathleen M. and Murphy, Stephanie T. and Seo, Youngho and Gullberg, Grant T.},
abstractNote = {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.},
doi = {10.1177/1536012117724558},
journal = {Molecular Imaging},
number = ,
volume = 16,
place = {United States},
year = {Wed Sep 06 00:00:00 EDT 2017},
month = {Wed Sep 06 00:00:00 EDT 2017}
}
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https://doi.org/10.1177/1536012117724558
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