PDF(Pubmed)
Abstract：
It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.
摘要：
已知导致氧化应激和甲状腺激素代谢功能障碍的炎症过程在与脂肪变性肝病(MASLD)相关的代谢功能障碍中高度改变。这项研究旨在解决鸟氨酸天冬氨酸（LOLA）和维生素E（VitE）在改善这些过程中的作用。成年Sprague-Dawley大鼠被分为五组，治疗28周：对照组（n=10）接受标准饮食（28周），并在第16至28周进行蒸馏水（DW）灌胃。MASLD组接受高脂肪和胆碱缺乏的饮食28周（MASLD组），并每天灌胃200mg/kg/天的LOLA，或每周两次，从16-28周使用150mgVitE。LOLA减少胶原沉积(p=0.006)。同样的处理减少了羰基，TBARS,巯基水平和GPx活性(p<0.001)。3型脱碘酶在MASLD组增加，下调T3控制的基因，在LOLA的存在下进行了纠正。LOLA还促进了复杂II的接近正常化，SDH,和GDH活性（p<0.001）和改善的网状应激，GRP78和HSPA9/GRP75蛋白水平降低（p<0.05）。增强甲状腺激素的能量产生和代谢，可能是因为LOLA的L-谷氨酸部分提供的GSH补充，为MASLD开辟了新的治疗途径。
