High-intensity interval training-induced metabolic adaptation coupled with an increase in Hif-1α and glycolytic protein expression

Abstract

It is known that repeated bouts of high-intensity interval training (HIIT) lead to enhanced levels of glycolysis, glycogenesis, and lactate transport proteins in skeletal muscle; however, little is known about the molecular mechanisms underlying these adaptations. To decipher the mechanism leading to improvement of skeletal muscle glycolytic capacity associated with HIIT, we examined the role of hypoxia-inducible factor-1α (Hif-1α), the major transcription factor regulating the expression of genes related to anaerobic metabolism, in the adaptation to HIIT. First, we induced Hif-1α accumulation using ethyl 3,4-dihydroxybenzoate (EDHB) to assess the potential role of Hif-1α in skeletal muscle. Treatment with EDHB significantly increased the protein levels of Hif-1α in gastrocnemius muscles, accompanied by elevated expression of genes related to glycolysis, glycogenesis, and lactate transport. Daily administration of EDHB for 1 wk resulted in elevated glycolytic enzyme activity in gastrocnemius muscles. Second, we examined whether a single bout of HIIT could induce Hif-1α protein accumulation and subsequent increase in the expression of genes related to anaerobic metabolism in skeletal muscle. We observed that the protein levels of Hif-1α and expression of the target genes were elevated 3 h after an acute bout of HIIT in gastrocnemius muscles. Last, we examined the effects of long-term HIIT. We found that long-term HIIT increased the basal levels of Hif-1α as well as the glycolytic capacity in gastrocnemius muscles. Our results suggest that Hif-1α is a key regulator in the metabolic adaptation to high-intensity training.

CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity

“…Hypoxia and the hypoxia inducible factors (HIF1α, HIF1β) can enhance glycolysis in response to high intensity training (Abe et al, 2015) or chronic hypoxia (for example high altitude) (Favier et al, 2015), which could contribute to increased power output in the context of exercise. Since we observed both increased liver glycogen depletion and enhanced transcriptional response to hypoxia during exercise in dKO mice, chronic enhancement of the hypoxia response may play a role in the altered exercise physiology of CRY-deficient animals.…”

Lactate as a Signaling Molecule That Regulates Exercise-Induced Adaptations

“…In glycolytic muscle fibers, the transcription factor hypoxia inducible factor-1 (HIF-1) activity is increased, particularly in response to high-intensity exercise [19]. This incremented activity generates many adaptations that include an increase in the anaerobic glycolytic capacity [20,21].…”

Hypoxic-Inflammatory Responses under Acute Hypoxia: In Vitro Experiments and Prospective Observational Expedition Trial

“…Mammalian responses to hypoxia in combination with either inflammation or exercise stress, are highly related and induce the same hypoxia-inducible-factor-1α (HIF-1α) signaling pathway [1][2][3][4][5][6]. In this regard, HIF-1α and its target genes are the key regulators allowing to adapt or even counteract hypoxic or inflammatory conditions [5,6].…”