Research Center of Translational Medicine, Jinan Central Hospital, Shandong University.
Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University.
J Oleo Sci. 2024;73(8):1069-1082. doi: 10.5650/jos.ess24055.
Diabetic liver injury (DLI) has raised attention in recent years. Liver injury results from type 2 diabetes mellitus (T2DM), and in turn accelerates T2DM development by exacerbating insulin resistance. However, effective approaches for mitigating DLI are surprisingly rare. Krill oil (KO) is an alternative source of omega-3 polyunsaturated fatty acids, possessing antioxidant and anti-inflammatory capacities. Here we investigated the effect of KO supplementation on DLI in a mouse model of T2DM induced by streptozotocin and high-fat diet. The diabetic mice developed glucose intolerance, elevated serum alanine aminotransferase and aspartate aminotransferase, and hepatic pathological injuries such as vacuolation, lipid accumulation and fibrosis deposition, the effects of which were mitigated by KO. Further investigation showed that KO ameliorated the DM-induced expression of fibrotic and inflammatory genes. Notably, KO dramatically reduced hepatic oxidative gene expression, lipid peroxidation and ROS production, all of which are hallmarks of ferroptosis. The inhibitory effect of KO on ferroptosis was confirmed by the KO-decreased hepatic expression of GPX4, COX2 and ACSL4, as well as the KO-reduced hepatic iron deposition. Further, KO restored hepatic NRF2 antioxidant signaling which combats ferroptosis. The present study may provide KO supplementation as a viable approach for the intervention of DLI.
近年来，糖尿病肝损伤（DLI）引起了人们的关注。肝损伤是由 2 型糖尿病（T2DM）引起的，反过来又通过加剧胰岛素抵抗加速 T2DM 的发展。然而，减轻 DLI 的有效方法却很少见。磷虾油（KO）是一种ω-3 多不饱和脂肪酸的替代来源，具有抗氧化和抗炎能力。在这里，我们研究了 KO 补充剂对链脲佐菌素和高脂肪饮食诱导的 T2DM 小鼠模型中 DLI 的影响。糖尿病小鼠表现出葡萄糖不耐受、血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶升高，以及肝病理损伤，如空泡化、脂质积累和纤维化沉积，这些都被 KO 减轻了。进一步的研究表明，KO 改善了 DM 诱导的纤维化和炎症基因的表达。值得注意的是，KO 显著降低了肝内氧化基因的表达、脂质过氧化和 ROS 产生，所有这些都是铁死亡的标志。KO 减少了肝内 GPX4、COX2 和 ACSL4 的表达，以及肝内铁沉积，从而证实了 KO 对铁死亡的抑制作用。此外，KO 恢复了肝脏的 NRF2 抗氧化信号，从而对抗铁死亡。本研究可能为 KO 补充剂作为干预 DLI 的一种可行方法提供了依据。
