Monocarboxylate transporter 4 deficiency enhances high‐intensity interval training‐induced metabolic adaptations in skeletal muscle

• DOI: 10.1113/jp285719
• Publication Date: 2024-03-21T18:24:14Z
• Authors: Yuki Tamura; Eunbin Jee; Karina Kouzaki; Takaya Kotani; Koichi Nakazato
• Keywords: Monocarboxylate transporter; Hexokinase; Endurance Training

Abstract High‐intensity exercise stimulates glycolysis, subsequently leading to elevated lactate production within skeletal muscle. While produced the muscle is predominantly released into circulation via monocarboxylate transporter 4 (MCT4), recent research underscores lactate's function as an intercellular and intertissue signalling molecule. However, its specific intracellular roles cells remains less defined. In this study, our objective was elucidate effects of increased intramuscular accumulation on adaptation training. To achieve this, we developed MCT4 knockout mice confirmed that a lack indeed results in pronounced during high‐intensity exercise. A key finding significant enhancement endurance capacity at high intensities when deficiency paired with interval training (HIIT). Furthermore, metabolic adaptations supportive enhanced were evident combination HIIT. Specifically, observed substantial uptick activity glycolytic enzymes, notably hexokinase, glycogen phosphorylase pyruvate kinase. The mitochondria also exhibited heightened oxidation capabilities, evidenced by increase oxygen consumption served substrate. This mitochondrial further substantiated dehydrogenase activity, isocitrate – rate‐limiting enzyme TCA cycle cytochrome c oxidase, pivotal electron transport chain. Our findings provide new insights physiological consequences exercises, deepening grasp molecular intricacies underpinning adaptation. image Key points We pioneered unique line (MCT4) specifically tailored ICR strain, optimal background for studies. exacerbates Pairing (HIIT) synergistic boost capacity, observable both organismal level (via treadmill running test) tissue (through ex vivo contractile test). Coordinating HIIT enhances activities oxidize pyruvate.