Abstract
[Purpose]Blood glucose and insulin resistance were lower following hypoxic exposure in previous studies. However, the effect of hypoxia as therapy in obese model has not been unknown.[Methods]Six-week-old mice were randomly divided into chow diet (n=10) and high-fat diet (HFD) groups (n=20). The chow diet group received a non-purified commercial diet (65 % carbohydrate, 21 % protein, and 14 % fat) and water ad libitum. The HFD group was fed an HFD (Research Diet, #D12492; 60% kcal from fat, 5.24 kcal/g). Both groups consumed their respective diet for 7 weeks. Subsequently, HFD-induced mice (12-weeks-old) were randomly divided into two treatment groups : HFD-Normoxia (HFD; n=10) and HFD-Hypoxia (HYP; n=10, fraction of inspired=14.6%). After treatment for 4 weeks, serum glucose, insulin and oral glucose tolerance tests (OGTT) were performed.[Results]Homeostatic model assessment values for insulin resistance (HOMA-IR) of the HYP group tended to be lower than the HFD group. Regarding the OGTT, the area under the curve was 13% lower for the HYP group than the HFD group.[Conclusion]Insulin resistance tended to be lower and glucose uptake capacity was significantly augmented under hypoxia. From a clinical perspective, exposure to hypoxia may be a practical method of treating obesity.
Highlights
Worldwide more than 1.4 billion adults are overweight, of which more than 400 million are obese[1]
We investigated the effects of hypoxic exposure on glycemic control in high-fat diet (HFD)-induced obese mice
We found that fasting blood insulin tended to be lower in the hypoxic exposed group (HYP) than the normoxia group (HFD)
Summary
Worldwide more than 1.4 billion adults are overweight, of which more than 400 million are obese[1]. Low hypoxia is defined as an altitude of 500-2,000 m (inspired oxygen fraction (FIO2) = 16.719.8%), moderate hypoxia is 2,000-3,000 m (FIO2 = 14.8-16.7%), high hypoxia is 3,000-5,500 m (FIO2 = 10.9-14.8%) and extreme hypoxia as >5,500 m (FIO2 < 10.9%)[4]. High altitude populations have lower blood glucose concentrations and a lower incidence of type 2 diabetes. Hill et al.[5] demonstrated that blood glucose concentration and insulin resistance were lower following gradual ascent in altitude (3,600-5,120 m). Woolcott et al.[6] reported that prolonged exposure to high hypoxia (altitude 3,500 m) might decrease concentration. Wang et al.[2] and Mackenzie et al.[7] reported that exposure to high-intermittent hypoxia (inspired oxygen fraction=14.6-14.7%) improved glycemic control. The capacity for glucose uptake is important. Hypoxia itself stimulates glucose uptake mediated by AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4) translocation[8,9]
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