Lactate induces the development of beige adipocytes via an increase in the level of reactive oxygen species

Abstract

Recent studies have indicated that lactate acts as a signaling molecule in various tissues. We previously demonstrated that intake of an amino acid mixture combined with exercise synergistically induced beige adipocyte formation in inguinal white adipose tissue (iWAT) in mice. Moreover, plasma lactate levels remained significantly elevated in the amino acid mixture + exercise group even 16 h after exercise, indicating that a lactate-mediated pathway may be involved in the induction of beige adipocyte formation. Against this background, we hypothesized that oral intake of lactate would induce beige adipocyte formation via the lactate signaling pathway without exercise. Furthermore, if oral intake of lactate can produce the same effect as exercise, lactate might be used as a food-derived exercise replacement-factor. Oral intake of lactate (100 mM in drinking water) for 4 weeks significantly induced beige adipocyte formation in iWAT in mice as well as a significant elevation of lactate transporter (monocarboxylic acid transporter 1; MCT1) and lactate dehydrogenase B levels. Administration of lactate to adipocytes significantly increased reactive oxygen species (ROS) and superoxide levels and the NADH/NAD⁺ ratio. The induction of lactate-mediated uncoupling protein 1 (UCP1) expression and ROS production were significantly suppressed by antioxidant treatment or inhibition of MCT1. However, UCP1 induction was not significantly affected by the inhibition of lactate receptor (hydroxycarboxylic acid receptor 1). These findings suggest that lactate-mediated ROS production induces beige adipocyte formation, and thus oral intake of lactate may confer some benefits of exercise without the need to perform exercise.