The anorectic and thermogenic effects of pharmacological lactate in male mice are confounded by treatment osmolarity and co-administered counterions

Jens Lund*, Alberte Wollesen Breum, Cláudia Gil, Sarah Falk, Frederike Sass, Marie Sophie Isidor, Oksana Dmytriyeva, Pablo Ranea-Robles, Cecilie Vad Mathiesen, Astrid Linde Basse, Olivia Sveidahl Johansen, Nicole Fadahunsi, Camilla Lund, Trine Sand Nicolaisen, Anders Bue Klein, Tao Ma, Brice Emanuelli, Maximilian Kleinert, Charlotte Mehlin Sørensen, Zachary Gerhart-Hines*Christoffer Clemmensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalNature Metabolism
Volume5
Issue number4
Pages (from-to)677-698
Number of pages22
ISSN2522-5812
DOIs
Publication statusPublished - 2023

Bibliographical note

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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