Effects of Hypoxic Preconditioning and Endurance Exercise on Circulating Fibroblast Growth Factor 21 in Mice

Endurance exercise and hypoxic exposure induce metabolic adaptations that influence energy substrate regulation. Circulating fibroblast growth factor 21 has emerged as an endocrine regulator of energy metabolism; however, whether prior hypoxic exposure modifies the fibroblast growth factor 21 response to subsequent exercise remains unclear. In this study, we investigated the effects of hypoxic preconditioning on circulating fibroblast growth factor 21 and metabolic responses in male C57BL/6J mice. Mice were assigned to four groups: normoxia, exercise after normoxia, hypoxia, and exercise after hypoxia. Hypoxic preconditioning consisted of 24-hour exposure to 13% oxygen followed by a single bout of endurance exercise under normoxic conditions. Plasma fibroblast growth factor 21 and metabolic parameters were measured, along with skeletal muscle glycogen and tissue fibroblast growth factor 21 levels. Circulating fibroblast growth factor 21 increased significantly following both hypoxia and exercise, whereas the fibroblast growth factor 21 protein content in the skeletal muscle and liver remained unchanged. Plasma glucose decreased under both conditions, insulin decreased with exercise, and free fatty acid concentrations were unchanged. Skeletal muscle glycogen content was reduced by both hypoxia and exercise. The expression of fibroblast growth factor 21-related genes remained unchanged. These findings indicate that hypoxic preconditioning and subsequent exercise exert independent main effects on circulating fibroblast growth factor 21, potentially reflecting an integrated endocrine response to metabolic stress rather than changes in local tissue expression.