Dietary d-Lactate Intake Facilitates Inflammatory Resolution by Modulating M1 Macrophage Polarization.

Abstract

SCOPE:

Given the d-lactate dehydrogenase (D-LDH) deficiency, L- but not d-lactate is assumed to be the physiological isomer in mammals. Paradoxically, many fermented foods (e.g., yogurt, sauerkraut, cheeses) often contain substantial amounts of d-lactate. In the present study, dietary d-lactate may be a previously unrecognized nutrient aiding in inflammatory resolution is hypothesized.

METHODS AND 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.

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.

• Authors: Yongheng Yan, Xiu Li, Qin Yang, Hao Zhang, Kasper Hettinga, Haitao Li, Wei Chen
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 66 Issue 24 Pg. e2200196 (12 2022) ISSN: 1613-4133 [Electronic] Germany
• PMID: 36239154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley-VCH GmbH.

Chemical References

• Anti-Inflammatory Agents
• Lactic Acid
• Receptors, G-Protein-Coupled

Topics

• Animals
• Mice
• Anti-Inflammatory Agents (pharmacology)
• Inflammation
• Lactic Acid
• Macrophages
• Mice, Knockout
• Receptors, G-Protein-Coupled (genetics)