Conclusion
This study highlights housekeeping function of the lactate-GPR81 axis in inflammation control, and suggests that dietary intake of d-lactate may underlie Metchnikoff's probiotic yogurt theory of life prolongation.
Results
The anti-inflammatory properties of d-lactate are evaluated in experimental colitis and endotoxemia. Oral administration of d-lactate favorably affects acute inflammation in two different mouse models. Analysis of lactate-the lactate receptor (the hydroxycarboxylic acid receptor 1 HCA1, formerly GPR81) signal axis in inflammation is performed in primary peritoneal macrophages and wild-type (WT) or GPR81 knockout (KO) mice. GPR81 KO mice are susceptible to endotoxic shock than WT mice, while d-lactate exerts its anti-inflammatory activities in a GPR81-dependent manner. Mechanistically, the activation of lactate-GPR81 axis may suppress LPS-TLR4 signaling to modulate M1 macrophage polarization. Although D-LDH deficiency in mammals impairs d-lactate clearance, it might prolong its plasma terminal half-life, and thus provide a pharmacokinetic advantage of d-lactate over l-lactate.