Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins

Abstract

The brain is capable of oxidizing lactate and ketone bodies through monocarboxylate transporters (MCTs). We examined the protein expression of MCT1, MCT2, MCT4, glucose transporter 1 (GLUT1), and cytochrome-c oxidase subunit IV (COX IV) in the rat brain within 24 h after a single exercise session. Brain samples were obtained from sedentary controls and treadmill-exercised rats (20 m/min, 8% grade). Acute exercise resulted in an increase in lactate in the cortex, hippocampus, and hypothalamus, but not the brainstem, and an increase in β-hydroxybutyrate in the cortex alone. After a 2-h exercise session MCT1 increased in the cortex and hippocampus 5 h postexercise, and the effect lasted in the cortex for 24 h postexercise. MCT2 increased in the cortex and hypothalamus 5-24 h postexercise, whereas MCT2 increased in the hippocampus immediately after exercise, and remained elevated for 10 h postexercise. Regional upregulation of MCT2 after exercise was associated with increases in brain-derived neurotrophic factor and tyrosine-related kinase B proteins, but not insulin-like growth factor 1. MCT4 increased 5-10 h postexercise only in the hypothalamus, and was associated with increased hypoxia-inducible factor-1α expression. However, none of the MCT isoforms in the brainstem was affected by exercise. Whereas GLUT 1 in the cortex increased only at 18 h postexercise, COX IV in the hippocampus increased 10 h after exercise and remained elevated for 24 h postexercise. These results suggest that acute prolonged exercise induces the brain region-specific upregulation of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.

Astrocytic glycogen-derived lactate fuels the brain during exhaustive exercise to maintain endurance capacity

“…1 and 3). These data are consistent with the increases in hippocampal MCT2 and cortical β-hydroxybutyrate during prolonged, but not exhaustive, exercise (15). Blood ketone bodies, at least β-hydroxybutyrate, could be transported to neurons by increased MCT2 to spare brain glycogen in exercise-exhausted rats.…”

“…We have reported a decrease in brain glycogen in the cortex, hippocampus, hypothalamus, cerebellum, and brainstem during prolonged exhaustive exercise associated with lactate elevation (13,14). Furthermore, prolonged, but not exhaustive, exercise increases levels of hippocampal MCT2 (15), which transports lactate to neurons as MCT1 does to exercising muscles (16). Although untested, it is thus postulated that the lactate derived from astrocytic glycogen plays a role in brain energetics to maintain endurance capacity during prolonged exercise, as is the case for memory formation in the hippocampus (6).…”

HO‐1 Is Essential for Tetrahydroxystilbene Glucoside Mediated Mitochondrial Biogenesis and Anti‐Inflammation Process in LPS‐Treated RAW264.7 Macrophages

“…COX-I and COX-IV are important members of the mitochondrial respiratory chain. Its protein expression and enzyme activity determined the capacity of ATP synthesis and electrons transfer [32]. In the current experiment, we observed an obvious increase of COX-IV protein as well as the COX-I activity in TSG treated RAW264.7 cells.…”

SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise

“…Exercise training also increases several neurotrophic factors in the hippocampus, including BDNF, which activate the PI3K signaling pathway (Cotman et al, 2007). Exercise has been shown to induce BDNF levels in the mediobasal hypothalamus (Takimoto and Hamada, 2014). In addition, we demonstrated that exercise training can increase mRNA expression of SF-1 and putative SF-1 target genes in the mediobasal hypothalamus (Figure 1—figure supplement 1).…”