Hyperoxia improves carbohydrate metabolism by browning of white adipocytes in obese type 2 diabetic rats

Abstract

AimsType 2 diabetes and obesity are associated with chronic hypoxia, which contributes to adipose tissue dysfunction and development of insulin resistance and metabolic disorders. We assessed long-term effects of hyperoxia on browning of adipocytes and carbohydrate metabolism in a murine model of type 2 diabetes. Main methodsMale Wistar rats (190–210 g) were divided into 4 groups: Control, O2-treated control, untreated diabetes, and O2-treated diabetes. Diabetes was induced using high-fat diet followed by a low-dose of streptozotocin (30 mg/kg). Hyperoxia sessions were included 2-h exposure to 95% oxygen, repeated 6 days/week for 5 weeks. Serum fasting glucose, insulin, lactate, and lipid profile were measured before, during, and after hyperoxia. Glucose and pyruvate tolerance tests, and histological evaluations of interscapular and epididymal fats were done at the end of study. Key findingsO2-treated diabetic rats compared to untreated ones, displayed lower weight gain, improved glucose-tolerance, insulin sensitivity, and more favorable lipid profile. In diabetic rats, hyperoxia increased surface area (6.36 ± 0.93 vs. 0.86 ± 0.16 mm2, P < 0.001), and volume density (1.53 ± 0.22 vs. 0.21 ± 0.04 mm3, P < 0.001) of interscapular adipose tissue; hyperoxia also increased protein levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in interscapular adipose tissue. The numerical density (541.7 ± 7.3 vs. 298.1 ± 11.7 mm3, P < 0.001) of epididymal fat were also higher. SignificanceThis study showed that beneficial metabolic effects of hyperoxia in obese type 2 diabetic rats including improved insulin sensitivity and glucose tolerance are at least in part due to browning of adipose tissue.