Neoagarotetraose Attenuates Hyperglycemia Through Inflammation Amelioration and Glucose Metabolism Improvement

ABSTRACT Dietary functional oligosaccharides exhibit anti‐inflammatory activity and regulatory impact on glucose metabolism. However, the protective effect of neoagarotetraose (NAT) against diabetes progression and the underlying molecular mechanisms remain unclear. This study investigated the hypoglycemic effect of NAT in diabetic mice. NAT was supplemented for 12 weeks in mice fed with a high‐fat diet (HFD). In HFD‐fed mice, NAT intervention (600 mg/kg) reduced the fasting glucose and insulin concentrations by 35.9% and 30.1% ( p < 0.01), and improved systemic inflammation and dyslipidemia. Moreover, diabetic mice induced by a high‐fat and high‐sugar diet plus streptozotocin were administered NAT for 7 weeks. NAT treatment lowered the area under the oral glucose and insulin tolerance test curves by 31.0% and 48.9% ( p < 0.01). NAT decreased the phosphorylation of nuclear factor kappa‐B to alleviate intestinal inflammation caused by diabetes mellitus. NAT reversed the derangements of hepatic glucose metabolism as evidenced by the activated AMPK/PGC‐1α signaling pathway and decreased mRNA expression of inflammatory factors. Furthermore, the imbalanced gut microbiota of diabetic mice was reshaped by NAT treatment. NAT attenuates hyperglycemia through inflammation amelioration and glucose metabolism improvement, thus mitigating the development of diabetes mellitus in mice.