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.

中文翻译：

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无机硝酸盐通过 XOR 催化的一氧化氮途径促进白色脂肪组织中的葡萄糖摄取和氧化分解代谢

全球人口老龄化、久坐不动的生活方式和不健康的饮食导致肥胖和 2 型糖尿病的发病率不断上升。这些代谢紊乱与一氧化氮 (NO) 信号紊乱和葡萄糖代谢受损有关。在绿叶蔬菜中发现的高浓度膳食无机硝酸盐可在体内转化为 NO，并在啮齿动物中显示出抗糖尿病和抗肥胖的特性。除了骨骼肌和肝脏等组织外，白色脂肪组织也是处理葡萄糖的重要生理部位。然而，控制硝酸盐对脂肪组织葡萄糖代谢影响的不同分子机制以及该组织对葡萄糖耐受表型的贡献仍有待确定。使用代谢组学和稳定同位素标记方法，结合转录分析，我们发现硝酸盐增加了硝酸盐处理大鼠的原代脂肪细胞和白色脂肪组织中的葡萄糖摄取和氧化分解代谢。从机制上讲，我们确定硝酸盐通过黄嘌呤氧化还原酶催化硝酸盐还原为 NO，并且独立于过氧化物酶体增殖物激活受体-α，从而诱导原代脂肪细胞发生这些表型变化。硝酸盐介导的白色脂肪组织中葡萄糖摄取和分解代谢的增强可能是该阴离子抗糖尿病作用的关键因素。我们确定硝酸盐通过黄嘌呤氧化还原酶催化硝酸盐还原为 NO 并独立于过氧化物酶体增殖物激活受体-α 诱导初级脂肪细胞的这些表型变化。硝酸盐介导的白色脂肪组织中葡萄糖摄取和分解代谢的增强可能是该阴离子抗糖尿病作用的关键因素。我们确定硝酸盐通过黄嘌呤氧化还原酶催化硝酸盐还原为 NO 并独立于过氧化物酶体增殖物激活受体-α 诱导初级脂肪细胞的这些表型变化。硝酸盐介导的白色脂肪组织中葡萄糖摄取和分解代谢的增强可能是该阴离子抗糖尿病作用的关键因素。