TY - JOUR
T1 - The anorectic and thermogenic effects of pharmacological lactate in male mice are confounded by treatment osmolarity and co-administered counterions
AU - Lund, Jens
AU - Breum, Alberte Wollesen
AU - Gil, Cláudia
AU - Falk, Sarah
AU - Sass, Frederike
AU - Isidor, Marie Sophie
AU - Dmytriyeva, Oksana
AU - Ranea-Robles, Pablo
AU - Mathiesen, Cecilie Vad
AU - Basse, Astrid Linde
AU - Johansen, Olivia Sveidahl
AU - Fadahunsi, Nicole
AU - Lund, Camilla
AU - Nicolaisen, Trine Sand
AU - Klein, Anders Bue
AU - Ma, Tao
AU - Emanuelli, Brice
AU - Kleinert, Maximilian
AU - Sørensen, Charlotte Mehlin
AU - Gerhart-Hines, Zachary
AU - Clemmensen, Christoffer
N1 - © 2023. The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - Lactate is a circulating metabolite and a signalling molecule with pleiotropic physiological effects. Studies suggest that lactate modulates energy balance by lowering food intake, inducing adipose browning and increasing whole-body thermogenesis. Yet, like many other metabolites, lactate is often commercially produced as a counterion-bound salt and typically administered in vivo through hypertonic aqueous solutions of sodium L-lactate. Most studies have not controlled for injection osmolarity and the co-injected sodium ions. Here, we show that the anorectic and thermogenic effects of exogenous sodium L-lactate in male mice are confounded by the hypertonicity of the injected solutions. Our data reveal that this is in contrast to the antiobesity effect of orally administered disodium succinate, which is uncoupled from these confounders. Further, our studies with other counterions indicate that counterions can have confounding effects beyond lactate pharmacology. Together, these findings underscore the importance of controlling for osmotic load and counterions in metabolite research.
AB - Lactate is a circulating metabolite and a signalling molecule with pleiotropic physiological effects. Studies suggest that lactate modulates energy balance by lowering food intake, inducing adipose browning and increasing whole-body thermogenesis. Yet, like many other metabolites, lactate is often commercially produced as a counterion-bound salt and typically administered in vivo through hypertonic aqueous solutions of sodium L-lactate. Most studies have not controlled for injection osmolarity and the co-injected sodium ions. Here, we show that the anorectic and thermogenic effects of exogenous sodium L-lactate in male mice are confounded by the hypertonicity of the injected solutions. Our data reveal that this is in contrast to the antiobesity effect of orally administered disodium succinate, which is uncoupled from these confounders. Further, our studies with other counterions indicate that counterions can have confounding effects beyond lactate pharmacology. Together, these findings underscore the importance of controlling for osmotic load and counterions in metabolite research.
U2 - 10.1038/s42255-023-00780-4
DO - 10.1038/s42255-023-00780-4
M3 - Journal article
C2 - 37055619
VL - 5
SP - 677
EP - 698
JO - Nature Metabolism
JF - Nature Metabolism
SN - 2522-5812
IS - 4
ER -