Risk Assessment Laboratory of Feed Derived Factors to Animal Product Quality Safety of Ministry of Agriculture & Rural Affairs, & National Engineering Research Center of Biological Feed, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Int J Mol Sci. 2021 Feb 1;22(3):1458. doi: 10.3390/ijms22031458.
Metabolic dysfunction-associated fatty liver disease (MAFLD) and its interaction with many metabolic pathways raises global public health concerns. This study aimed to determine the therapeutic effects of Pyrroloquinoline quinone (PQQ, provided by PQQ.Na) on MAFLD in a chick model and primary chicken hepatocytes with a focus on lipid metabolism, anti-oxidative capacity, and mitochondrial biogenesis. The MAFLD chick model was established on laying hens by feeding them a high-energy low-protein (HELP) diet. Primary hepatocytes isolated from the liver of laying hens were induced for steatosis by free fatty acids (FFA) and for oxidative stress by hydrogen peroxide (HO). In the MAFLD chick model, the dietary supplementation of PQQ conspicuously ameliorated the negative effects of the HELP diet on liver biological functions, suppressed the progression of MAFLD mainly through enhanced lipid metabolism and protection of liver from oxidative injury. In the steatosis and oxidative stress cell models, PQQ functions in the improvement of the lipid metabolism and hepatocytes tolerance to fatty degradation and oxidative damage by enhancing mitochondrial biogenesis and then increasing the anti-oxidative activity and anti-apoptosis capacity. At both the cellular and individual levels, PQQ was demonstrated to exert protective effects of hepatocyte and liver from fat accumulation through the improvement of mitochondrial biogenesis and maintenance of redox homeostasis. The key findings of the present study provide an in-depth knowledge on the ameliorative effects of PQQ on the progression of fatty liver and its mechanism of action, thus providing a theoretical basis for the application of PQQ, as an effective nutrient, into the prevention of MAFLD.
代谢相关脂肪性肝病(MAFLD)及其与多种代谢途径的相互作用引起了全球公共卫生的关注。本研究旨在确定吡咯喹啉醌(PQQ,由 PQQ.Na 提供)在鸡模型和原代鸡肝细胞中对 MAFLD 的治疗作用,重点关注脂质代谢、抗氧化能力和线粒体生物发生。通过给产蛋母鸡喂食高能低蛋白(HELP)饮食来建立 MAFLD 鸡模型。从产蛋母鸡肝脏中分离的原代肝细胞通过游离脂肪酸(FFA)诱导脂肪变性,通过过氧化氢(HO)诱导氧化应激。在 MAFLD 鸡模型中,饮食补充 PQQ 显著改善了 HELP 饮食对肝脏生物功能的负面影响,主要通过增强脂质代谢和保护肝脏免受氧化损伤来抑制 MAFLD 的进展。在脂肪变性和氧化应激细胞模型中,PQQ 通过增强线粒体生物发生来改善脂质代谢和肝细胞对脂肪降解和氧化损伤的耐受性,从而增加抗氧化活性和抗凋亡能力,从而发挥作用。在细胞和个体水平上,PQQ 通过改善线粒体生物发生和维持氧化还原稳态,显示出对肝细胞和肝脏免受脂肪堆积的保护作用。本研究的主要发现深入了解了 PQQ 对脂肪肝进展的改善作用及其作用机制,为将 PQQ 作为一种有效的营养物质应用于 MAFLD 的预防提供了理论依据。