United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203.
United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203.
J Nutr Biochem. 2020 Apr;78:108336. doi: 10.1016/j.jnutbio.2019.108336. Epub 2020 Jan 8.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries, and the gut-liver axis is implicated in liver disease pathogenesis. We hypothesize that advanced liver steatosis accompanies an increase in hepatic inflammation, colonic secondary bile acids (BAs) and secondary BA-producing bacteria in mice fed a high-fat (HF) diet model of obesity. Four-week old male C57BL/6 mice were fed an HF (45% energy) or a low-fat (LF) (10% energy) diet for 21 weeks. At the end of the study, body weight and body fat percentage in the HF group were 0.23- and 0.41-fold greater than those in the LF group, respectively. Similarly, the HF group exhibited an increase in hepatic lipid droplets, inflammatory cell infiltration, inducible nitric oxide synthase, and hepatocellular ballooning (but without hepatic Mallory bodies) which are key histological features of advanced hepatic steatosis. Furthermore, RNA sequencing, qPCR and immunohistological methods found that nicotinamide n-methyltransferase and selenoprotein P, two inflammation-related hepatic genes, were upregulated in the HF group. Consistent with the hepatic inflammation, the levels of proinflammatory plasma-cytokines (TNF-α and IL6), colonic secondary BAs (LCA, DCA) and secondary BA producing bacteria (e.g., lactobacillaceae/Lachnospiraceae) were at least 0.5-fold greater in the HF group compared with the LF group. Taken together, the data demonstrate that advanced liver-steatosis is concurrent with an elevated level of hepatic inflammation, colonic secondary bile acids and their associated bacteria in mice fed an HF diet. These data suggest a potential gut-liver crosstalk at the stage of advanced liver-steatosis.
非酒精性脂肪性肝病（NAFLD）是西方国家最常见的慢性肝病，肠道-肝脏轴与肝病的发病机制有关。我们假设在肥胖的高脂肪（HF）饮食模型中，肝脂肪变性加重伴随着肝炎症、结肠次级胆汁酸（BAs）和次级 BA 产生菌的增加。4 周龄雄性 C57BL/6 小鼠喂食 HF（45%能量）或 LF（10%能量）饮食 21 周。在研究结束时，HF 组的体重和体脂百分比分别比 LF 组高 0.23 倍和 0.41 倍。同样，HF 组表现出肝脂肪滴、炎症细胞浸润、诱导型一氧化氮合酶和肝细胞气球样变（但无肝 Mallory 小体）的增加，这些都是晚期肝脂肪变性的关键组织学特征。此外，RNA 测序、qPCR 和免疫组织化学方法发现，两种与炎症相关的肝基因烟酰胺 N-甲基转移酶和硒蛋白 P 在 HF 组中上调。与肝炎症一致，促炎血浆细胞因子（TNF-α和 IL6）、结肠次级 BAs（LCA、DCA）和次级 BA 产生菌（如乳杆菌科/lachnospiraceae）的水平在 HF 组中至少比 LF 组高 0.5 倍。总之，这些数据表明，在喂食 HF 饮食的小鼠中，晚期肝脂肪变性与肝炎症、结肠次级胆汁酸及其相关细菌水平升高有关。这些数据表明在晚期肝脂肪变性阶段存在潜在的肠道-肝脏串扰。
