Contribution of High-Intensity Interval Exercise in the Fasted State to Fat Browning: Potential Roles of Lactate and -Hydroxybutyrate

Purpose: Fat browning contributes to energy consumption and may have metabolic benefits against obesity; however, the potential roles of lactate and beta-hydroxybutyrate (beta-HB) in fat browning remain unclear. We investigated the roles of a single bout of aerobic exercise that increases lactate and beta-HB levels in the fasted state on the regulation of fat browning in rats and humans. Methods: Male Sprague-Dawley rats were exposed to 24-h fasting and/or a single bout moderate-intensity aerobic exercise (40 min): sedentary (CON), exercise (ND-EX), fasting (FAST), and exercise + fasting (F-EX). Adult men (n = 13) were randomly assigned into control with food intake (CON), exercise with intensity at onset of blood lactate accumulation in the fasted state (F-OBLA), and high-intensity interval exercise in the fasted state (F-HIIE) until each participant expended 350 kcal of energy. For evaluating the effects of exercise intensity in rats, we conducted another set of animal experiment, including groups of sedentary fed control, fasting control, and exercise with moderate-intensity or HIIE for 40 min after a 24-h fasting. Results: Regardless of fasting, single bout of exercise increases the concentration of lactate and beta-HB in rats, but the exercise in the fasted state increases the beta-HB level more significantly in rats and humans. F-EX-activated fat browning (AMPK-SirT1- PGC1a pathway and PRDM16) and thermogenic factor (UCP1) in white fat of rats. In rats and humans, exercise in the fasted state increased the blood levels of fat browning-related adipomyokines. In particular, compared with F-OBLA, F-HIIE more efficiently increases free fatty acid as well as blood levels of fat browning adipomyokines in humans, which was correlated with blood levels of lactate and beta-HB. In rats that performed exercise with different intensity, the higher plasma lactate and beta-HB levels, and higher expression of p-AMPK, UCP1, and PRDM16 in white adipose tissue of HIIE group than those of moderate-intensity group, were observed. Conclusions: A single bout of aerobic exercise in the fasted state significantly induced fat browning-related pathways, free fatty acid, and adipomyokines, particularly F-HIIE in human. Although further evidence for supporting our results is required in humans, aerobic exercise in the fasted state with high intensity that increase lactate and beta-HB may be a modality of fat browning.