D-阿洛酮糖,一种稀有的糖,已经提出在解决代谢紊乱如肥胖和2型糖尿病(T2D)方面具有潜在的益处。然而,这些影响背后的确切机制仍然知之甚少。我们旨在阐明D-阿洛酮糖影响肥胖诱导的胰岛素抵抗的机制。我们对暴露于高脂饮食(HFD)的小鼠的肝脏和白色脂肪组织以及肥胖个体的白色脂肪组织进行了基因集富集分析。我们的研究表明,D-阿洛酮糖有效抑制IFN-γ,恢复趋化因子信号,和增强HFD喂养小鼠肝脏中的巨噬细胞功能。这意味着D-阿洛酮糖可以抑制肝脏炎症,减轻胰岛素抵抗并随后影响脂肪组织。此外,D-阿洛酮糖的补充改善了HFD喂养的小鼠的肝脏和白色脂肪组织中的线粒体NADH稳态和翻译。值得注意的是,我们观察到,与胰岛素敏感型肥胖受试者相比,胰岛素抵抗型肥胖受试者的网膜组织中NADH稳态和线粒体翻译降低.一起来看,这些结果表明,补充阿洛酮糖可通过减轻巨噬细胞和线粒体功能的破坏,改善肥胖诱导的胰岛素抵抗.此外,我们的数据强化了线粒体能量消耗在肥胖引发的胰岛素抵抗发展中的关键作用.
D-allulose, a rare sugar, has been proposed to have potential benefits in addressing metabolic disorders such as obesity and type 2 diabetes (T2D). However, the precise mechanisms underlying these effects remain poorly understood. We aimed to elucidate the mechanisms by which D-allulose influences obesity-induced insulin resistance. We conducted gene set enrichment analysis on the liver and white adipose tissue of mice exposed to a high-fat diet (HFD) along with the white adipose tissue of individuals with obesity. Our study revealed that D-allulose effectively suppressed IFN-γ, restored chemokine signaling, and enhanced macrophage function in the livers of HFD-fed mice. This implies that D-allulose curtails liver inflammation, alleviating insulin resistance and subsequently impacting adipose tissue. Furthermore, D-allulose supplementation improved mitochondrial NADH homeostasis and translation in both the liver and white adipose tissue of HFD-fed mice. Notably, we observed decreased NADH homeostasis and mitochondrial translation in the omental tissue of insulin-resistant obese subjects compared to their insulin-sensitive counterparts. Taken together, these results suggest that supplementation with allulose improves obesity-induced insulin resistance by mitigating the disruptions in macrophage and mitochondrial function. Furthermore, our data reinforce the crucial role that mitochondrial energy expenditure plays in the development of insulin resistance triggered by obesity.