Abstract
Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions.Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspiredO2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspiredO2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle.Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP;1.9±0.9vs.−0.3±0.9;p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1αprotein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group.Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.
Highlights
According to the International Society for Mountain Medicine, high altitude is defined as 3,000-5,500 m above sea level and extreme altitude as >5,500 m above sea level
We explored changes in the expression levels of enzymes related to carbohydrate oxidation (e.g., hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), and pyruvate dehydrogenase kinase 4 (PDK4)) and a regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)) to elucidate potential mechanisms responsible for any observed changes
Body weight gains were significantly lower in the hypoxia group (HYP) group than in the control group (CON) group (CON vs. HYP; 1:9 ± 0:9 vs. −0:3 ± 0:9 g; p < 0:001)
Summary
Other studies have found that prolonged exposure to high altitude (3,500 m) may decrease blood glucose [5]. Deer mice expend significantly more energy per day than mice living lowland, which would require a high rate of O2 consumption. These mice may rely on carbohydrates as a substrate because of the relatively high yield of ATP per mole of O2 consumed in carbohydrate metabolism [7]. Enhanced carbohydrate oxidation following exposure to hypoxia (at 4,300–4,540 m) is expected, as previous studies have demonstrated that healthy humans exhibit increased levels of glucose disposal at high altitudes compared to sea level altitudes [8, 9].
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