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

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.

 

Comments：

The passage discusses the physiological effects of lactate as a signalling molecule and its potential to modulate energy balance. However, commercial lactate is often administered in vivo as a counterion-bound salt in hypertonic aqueous solutions of sodium L-lactate, which can confound the results of studies that investigate lactate's effects. The hypertonicity of the injected solutions and the co-injected sodium ions can mask or exaggerate the effects of lactate. The passage presents evidence that the anorectic and thermogenic effects of exogenous sodium L-lactate in male mice are confounded by the osmolarity of the injected solutions. On the other hand, orally administered disodium succinate's anti-obesity effect is not affected by these confounders. The passage concludes that counterions can have confounding effects beyond lactate pharmacology, emphasizing the need to control for osmotic load and counterions in metabolite research.

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S6010	Sodium L-lactate	Sodium L-lactate is used as a food additive, preservative, acidity regulator and bulking agent.

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