Dataset Information

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-¹³ C]-l-lactate.

ABSTRACT:

Purpose

To evaluate the utility of hyperpolarized [1-¹³ C]-l-lactate to detect hepatic pyruvate carboxylase activity in vivo under fed and fasted conditions.

Methods

[1-¹³ C]-labeled sodium L-lactate was polarized using a dynamic nuclear polarizer. Polarization level and the T₁ were measured in vitro in a 3 Telsa MR scanner. Two groups of healthy rats (fasted vs. fed) were prepared for in vivo studies. Each rat was anesthetized and intravenously injected with 60-mM hyperpolarized [1-¹³ C]-l-lactate, immediately followed by dynamic acquisition of ¹³ C (carbon-13) MR spectra from the liver at 3 Tesla. The dosage-dependence of the ¹³ C-products was also investigated by performing another injection of an equal volume of 30-mM hyperpolarized [1-¹³ C]-l-lactate.

Results

T₁ and liquid polarization level of [1-¹³ C]-l-lactate were estimated as 67.8 s and 40.0%, respectively. [1-¹³ C]pyruvate and [1-¹³ C]alanine, [¹³ C]bicarbonate ( HCO3- ) and [1-¹³ C]aspartate were produced from hyperpolarized [1-¹³ C]-l-lactate in rat liver. Smaller HCO3- and larger aspartate were measured in the fed group compared to the fasted group. Pyruvate and alanine production were increased in proportion to the lactate concentration, whereas the amount of HCO3- and aspartate production was consistent between 30-mM and 60-mM lactate injections.

Conclusion

This study demonstrates that a unique biomarker of pyruvate carboxylase flux, the appearance of [1-¹³ C]aspartate from [1-¹³ C]-l-lactate, is sensitive to nutritional state and may be monitored in vivo at 3 Tesla. Because [¹³ C] HCO3- is largely produced by pyruvate dehydrogenase flux, these results suggest that the ratio of [1-¹³ C]aspartate and [¹³ C] HCO3- (aspartate/ HCO3- ) reflects the saturable pyruvate carboxylase/pyruvate dehydrogenase enzyme activities.

SUBMITTER: Chen J

PROVIDER: S-EPMC7718288 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-<sup>13</sup> C]-l-lactate.

Chen Jun J Hackett Edward P EP Kovacs Zoltan Z Malloy Craig R CR Park Jae Mo JM

Magnetic resonance in medicine 20200916 3

<h4>Purpose</h4>To evaluate the utility of hyperpolarized [1-<sup>13</sup> C]-l-lactate to detect hepatic pyruvate carboxylase activity in vivo under fed and fasted conditions.<h4>Methods</h4>[1-<sup>13</sup> C]-labeled sodium L-lactate was polarized using a dynamic nuclear polarizer. Polarization level and the T<sub>1</sub> were measured in vitro in a 3 Telsa MR scanner. Two groups of healthy rats (fasted vs. fed) were prepared for in vivo studies. Each rat was anesthetized and intravenously in ...[more]

PMID: 32936474

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Dataset Information

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-¹³ C]-l-lactate.

Purpose

Methods

Results

Conclusion

Publications

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-<sup>13</sup> C]-l-lactate.

Similar Datasets

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Dataset Information

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-13 C]-l-lactate.

Purpose

Methods

Results

Conclusion

Publications

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-<sup>13</sup> C]-l-lactate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Assessment of hepatic pyruvate carboxylase activity using hyperpolarized [1-¹³ C]-l-lactate.