Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control; College of Food Science and Technology , Nanjing Agricultural University , Nanjing , 210095 , China.
J Agric Food Chem. 2019 Aug 14;67(32):8794-8809. doi: 10.1021/acs.jafc.9b03136. Epub 2019 Aug 6.
Oxidative stress may play a critical role in the progression of liver disorders. Increasing interest has been given to the associations among diet, oxidative stress, gut-liver axis, and nonalcoholic fatty liver disease. Here, we investigated the effects of processed meat proteins on biomarkers of lipid homeostasis, hepatic metabolism, antioxidant functions, and gut microbiota composition in glutaredoxin1 deficient (Glrx1) mice. The wild-type (WT) and Glrx1 mice were fed a soy protein diet (SPD), a dry-cured pork protein diet (DPD), a braised pork protein diet (BPD), and a cooked pork protein diet (CPD) at a dose of 20% of protein for 3 months. Serum and hepatic total cholesterol, serum endotoxin, hepatic liver droplet %, and antioxidant capacity were significantly increased in the CPD fed WT mice. In addition, CPD fed Glrx1 mice significantly increased total cholesterol, triacylglycerol, and pro-inflammatory cytokines which are accompanied by higher steatosis scores, intrahepatic lipid accumulation, and altered gene expression associated with lipid metabolism. Furthermore, hepatic gene expression of Nrf2/keap1 signaling pathway and its downstream signaling targets were determined using RT-qPCR. Glrx1 deficiency increased Nrf2 activity and expression of its target genes (GPx, catalase, SOD1, G6pd, and Bbc3), which was exacerbated by intake of CPD. Metagenomic analyses revealed that Glrx1 mice fed meat protein diets had higher abundances of , , and but lower abundances of , , and than their wild-type counterparts. In summary, Glrx1 deficiency induced an increase in serum biomarkers for lipid homeostasis, gut microbiota imbalance, and upregulation of Nrf2/Keap1 and antioxidant defense genes, which was aggravated by cooked meat protein diet.
氧化应激可能在肝脏疾病的进展中起关键作用。人们越来越关注饮食、氧化应激、肠道-肝脏轴和非酒精性脂肪性肝病之间的关系。在这里，我们研究了加工肉蛋白对谷氧还蛋白 1 缺陷 (Glrx1) 小鼠脂类稳态、肝脏代谢、抗氧化功能和肠道微生物组成的影响。野生型 (WT) 和 Glrx1 小鼠分别用大豆蛋白饮食 (SPD)、干腌猪肉蛋白饮食 (DPD)、红烧猪肉蛋白饮食 (BPD) 和熟猪肉蛋白饮食 (CPD) 喂养，蛋白含量为 20%，喂养 3 个月。CPD 喂养的 WT 小鼠血清和肝脏总胆固醇、血清内毒素、肝脏脂肪滴 %和抗氧化能力显著增加。此外，CPD 喂养的 Glrx1 小鼠总胆固醇、三酰甘油和促炎细胞因子显著增加，伴随着更高的脂肪变性评分、肝内脂质积累和与脂质代谢相关的基因表达改变。此外，还使用 RT-qPCR 测定了 Nrf2/keap1 信号通路及其下游信号靶基因在肝组织中的基因表达。Glrx1 缺乏增加了 Nrf2 活性和其靶基因 (GPx、过氧化氢酶、SOD1、G6pd 和 Bbc3) 的表达，而 CPD 的摄入加剧了这种情况。宏基因组分析显示，用肉蛋白饮食喂养的 Glrx1 小鼠的 、 和 的丰度较高，而 、 和 的丰度较低。总之，Glrx1 缺乏导致血清脂质稳态标志物增加、肠道微生物失衡以及 Nrf2/Keap1 和抗氧化防御基因上调，而熟肉蛋白饮食加剧了这种情况。
