Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate

Rasmus N Ottosen; Jacob M Seefeldt; Jakob Hansen; Roni Nielsen; Niels Møller; Mogens Johannsen; Thomas B Poulsen

doi:10.1021/acs.jafc.4c04849

Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate

Rasmus N Ottosen, Jacob M Seefeldt, Jakob Hansen, Roni Nielsen, Niels Møller^*, Mogens Johannsen^*, Thomas B Poulsen^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Elevation of the plasma levels of ( S)-lactate (Lac) and/or ( R)-beta-hydroxybutyrate (BHB) occurs naturally in response to strenuous exercise and prolonged fasting, respectively, resulting in millimolar concentrations of these two metabolites. It is increasingly appreciated that Lac and BHB have wide-ranging beneficial physiological effects, suggesting that novel nutritional solutions, compatible with high-level and/or sustained consumption, which allow direct control of plasma levels of Lac and BHB, are of strong interest. In this study, we present a molecular hybrid between ( S)-lactate and the BHB-precursor ( R)-1,3-butanediol in the form of a simple ester referred to as LaKe . We show that LaKe can be readily prepared on the kilogram scale and undergoes rapid hydrolytic conversion under a variety of physiological conditions to release its two constituents. Oral ingestion of LaKe , in rats, resulted in dose-dependent elevation of plasma levels of Lac and BHB triggering expected physiological responses such as reduced lipolysis and elevation of the appetite-suppressing compound N-L-lactoyl-phenylalanine (Lac-Phe).

Original language	English
Journal	Journal of Agricultural and Food Chemistry
Volume	72
Issue	36
Pages (from-to)	19883-19890
Number of pages	8
ISSN	0021-8561
DOIs	https://doi.org/10.1021/acs.jafc.4c04849
Publication status	Published - 11 Sept 2024

Keywords

N-
appetite regulation
exercise mimetics
exerkine
ketones
lactate

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10.1021/acs.jafc.4c04849

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title = "Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate",

abstract = "Elevation of the plasma levels of ( S)-lactate (Lac) and/or ( R)-beta-hydroxybutyrate (BHB) occurs naturally in response to strenuous exercise and prolonged fasting, respectively, resulting in millimolar concentrations of these two metabolites. It is increasingly appreciated that Lac and BHB have wide-ranging beneficial physiological effects, suggesting that novel nutritional solutions, compatible with high-level and/or sustained consumption, which allow direct control of plasma levels of Lac and BHB, are of strong interest. In this study, we present a molecular hybrid between ( S)-lactate and the BHB-precursor ( R)-1,3-butanediol in the form of a simple ester referred to as LaKe . We show that LaKe can be readily prepared on the kilogram scale and undergoes rapid hydrolytic conversion under a variety of physiological conditions to release its two constituents. Oral ingestion of LaKe , in rats, resulted in dose-dependent elevation of plasma levels of Lac and BHB triggering expected physiological responses such as reduced lipolysis and elevation of the appetite-suppressing compound N-L-lactoyl-phenylalanine (Lac-Phe). ",

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author = "Ottosen, {Rasmus N} and Seefeldt, {Jacob M} and Jakob Hansen and Roni Nielsen and Niels M{\o}ller and Mogens Johannsen and Poulsen, {Thomas B}",

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doi = "10.1021/acs.jafc.4c04849",

language = "English",

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Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate. / Ottosen, Rasmus N; Seefeldt, Jacob M ; Hansen, Jakob et al.
In: Journal of Agricultural and Food Chemistry, Vol. 72, No. 36, 11.09.2024, p. 19883-19890.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate

AU - Ottosen, Rasmus N

AU - Seefeldt, Jacob M

AU - Hansen, Jakob

AU - Nielsen, Roni

AU - Møller, Niels

AU - Johannsen, Mogens

AU - Poulsen, Thomas B

PY - 2024/9/11

Y1 - 2024/9/11

N2 - Elevation of the plasma levels of ( S)-lactate (Lac) and/or ( R)-beta-hydroxybutyrate (BHB) occurs naturally in response to strenuous exercise and prolonged fasting, respectively, resulting in millimolar concentrations of these two metabolites. It is increasingly appreciated that Lac and BHB have wide-ranging beneficial physiological effects, suggesting that novel nutritional solutions, compatible with high-level and/or sustained consumption, which allow direct control of plasma levels of Lac and BHB, are of strong interest. In this study, we present a molecular hybrid between ( S)-lactate and the BHB-precursor ( R)-1,3-butanediol in the form of a simple ester referred to as LaKe . We show that LaKe can be readily prepared on the kilogram scale and undergoes rapid hydrolytic conversion under a variety of physiological conditions to release its two constituents. Oral ingestion of LaKe , in rats, resulted in dose-dependent elevation of plasma levels of Lac and BHB triggering expected physiological responses such as reduced lipolysis and elevation of the appetite-suppressing compound N-L-lactoyl-phenylalanine (Lac-Phe).

AB - Elevation of the plasma levels of ( S)-lactate (Lac) and/or ( R)-beta-hydroxybutyrate (BHB) occurs naturally in response to strenuous exercise and prolonged fasting, respectively, resulting in millimolar concentrations of these two metabolites. It is increasingly appreciated that Lac and BHB have wide-ranging beneficial physiological effects, suggesting that novel nutritional solutions, compatible with high-level and/or sustained consumption, which allow direct control of plasma levels of Lac and BHB, are of strong interest. In this study, we present a molecular hybrid between ( S)-lactate and the BHB-precursor ( R)-1,3-butanediol in the form of a simple ester referred to as LaKe . We show that LaKe can be readily prepared on the kilogram scale and undergoes rapid hydrolytic conversion under a variety of physiological conditions to release its two constituents. Oral ingestion of LaKe , in rats, resulted in dose-dependent elevation of plasma levels of Lac and BHB triggering expected physiological responses such as reduced lipolysis and elevation of the appetite-suppressing compound N-L-lactoyl-phenylalanine (Lac-Phe).

KW - N-

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KW - exercise mimetics

KW - exerkine

KW - ketones

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DO - 10.1021/acs.jafc.4c04849

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JF - Journal of Agricultural and Food Chemistry

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ER -

Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate

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