Inorganic Nitrate Promotes Glucose Uptake and Oxidative Catabolism in White Adipose Tissue Through the XOR-Catalyzed Nitric Oxide Pathway.
Ben D McNallyAmy MoranNicole T WattTom AshmoreAnna WhiteheadSteven A MurfittMark T KearneyRichard M CubbonAndrew J MurrayJulian L GriffinLee D RobertsPublished in: Diabetes (2020)
An aging global population combined with sedentary lifestyles and unhealthy diets has contributed to an increasing incidence of obesity and type 2 diabetes. These metabolic disorders are associated with perturbations to nitric oxide (NO) signaling and impaired glucose metabolism. Dietary inorganic nitrate, found in high concentration in green leafy vegetables, can be converted to NO in vivo and demonstrates antidiabetic and antiobesity properties in rodents. Alongside tissues including skeletal muscle and liver, white adipose tissue is also an important physiological site of glucose disposal. However, the distinct molecular mechanisms governing the effect of nitrate on adipose tissue glucose metabolism and the contribution of this tissue to the glucose-tolerant phenotype remain to be determined. Using a metabolomic and stable-isotope labeling approach, combined with transcriptional analysis, we found that nitrate increases glucose uptake and oxidative catabolism in primary adipocytes and white adipose tissue of nitrate-treated rats. Mechanistically, we determined that nitrate induces these phenotypic changes in primary adipocytes through the xanthine oxidoreductase-catalyzed reduction of nitrate to NO and independently of peroxisome proliferator-activated receptor-α. The nitrate-mediated enhancement of glucose uptake and catabolism in white adipose tissue may be a key contributor to the antidiabetic effects of this anion.
Keyphrases
- adipose tissue
- nitric oxide
- insulin resistance
- drinking water
- nitric oxide synthase
- type diabetes
- high fat diet
- hydrogen peroxide
- skeletal muscle
- blood glucose
- gene expression
- metabolic syndrome
- physical activity
- cardiovascular disease
- weight loss
- risk assessment
- high fat diet induced
- transcription factor
- blood pressure
- risk factors
- room temperature
- body mass index
- glycemic control
- ionic liquid
- health risk
- oxidative stress