Detection of myocardial medium-chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1-<sup>13</sup> C]octanoate.

Details

Ressource 1Request a copy Under indefinite embargo.
UNIL restricted access
State: Public
Version: author
License: Not specified
Serval ID
serval:BIB_E1EE7E8183A2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Detection of myocardial medium-chain fatty acid oxidation and tricarboxylic acid cycle activity with hyperpolarized [1-<sup>13</sup> C]octanoate.
Journal
NMR in biomedicine
Author(s)
Yoshihara HAI, Bastiaansen JAM, Karlsson M., Lerche M.H., Comment A., Schwitter J.
ISSN
1099-1492 (Electronic)
ISSN-L
0952-3480
Publication state
Published
Issued date
06/01/2020
Peer-reviewed
Oui
Pages
e4243
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Under normal conditions, the heart mainly relies on fatty acid oxidation to meet its energy needs. Changes in myocardial fuel preference are noted in the diseased and failing heart. The magnetic resonance signal enhancement provided by spin hyperpolarization allows the metabolism of substrates labeled with carbon-13 to be followed in real time in vivo. Although the low water solubility of long-chain fatty acids abrogates their hyperpolarization by dissolution dynamic nuclear polarization, medium-chain fatty acids have sufficient solubility to be efficiently polarized and dissolved. In this study, we investigated the applicability of hyperpolarized [1- <sup>13</sup> C]octanoate to measure myocardial medium-chain fatty acid metabolism in vivo. Scanning rats infused with a bolus of hyperpolarized [1- <sup>13</sup> C]octanoate, the primary metabolite observed in the heart was identified as [1- <sup>13</sup> C]acetylcarnitine. Additionally, [5- <sup>13</sup> C]glutamate and [5- <sup>13</sup> C]citrate could be respectively resolved in seven and five of 31 experiments, demonstrating the incorporation of oxidation products of octanoate into the tricarboxylic acid cycle. A variable drop in blood pressure was observed immediately following the bolus injection, and this drop correlated with a decrease in normalized acetylcarnitine signal (acetylcarnitine/octanoate). Increasing the delay before infusion moderated the decrease in blood pressure, which was attributed to the presence of residual gas bubbles in the octanoate solution. No significant difference in normalized acetylcarnitine signal was apparent between fed and 12-hour fasted rats. Compared with a solution in buffer, the longitudinal relaxation of [1- <sup>13</sup> C]octanoate was accelerated ~3-fold in blood and by the addition of serum albumin. These results demonstrate the potential of hyperpolarized [1- <sup>13</sup> C]octanoate to probe myocardial medium-chain fatty acid metabolism as well as some of the limitations that may accompany its use.
Keywords
13C-MRS, beta-oxidation, cardiac, dissolution dynamic nuclear polarization, hyperpolarization, medium-chain triglyceride, serum albumin
Pubmed
Web of science
Create date
10/01/2020 15:51
Last modification date
17/10/2020 6:26
Usage data