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

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-

KW - appetite regulation

KW - exercise mimetics

KW - exerkine

KW - ketones

KW - lactate

UR - http://www.scopus.com/inward/record.url?scp=85202707190&partnerID=8YFLogxK

U2 - 10.1021/acs.jafc.4c04849

DO - 10.1021/acs.jafc.4c04849

M3 - Journal article

C2 - 39214666

SN - 0021-8561

VL - 72

SP - 19883

EP - 19890

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

IS - 36

ER -