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，肠肝轴与肝病的发病机制有关。我们假设，在肥胖的高脂饮食模型中，晚期肝脂肪变性伴随着肝脏炎症，结肠次要胆汁酸（BAs）和继发BA产生细菌的增加。给四周大的雄性C57BL / 6小鼠喂食HF（45％能量）或低脂（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组的肝脂质滴增加，炎症细胞浸润，诱导型一氧化氮合酶，和肝细胞膨胀（但没有肝马洛体），这是晚期肝脂肪变性的关键组织学特征。此外，RNA测序，qPCR和免疫组织学方法发现，HF组中两个与炎症相关的肝基因烟酰胺n-甲基转移酶和硒蛋白P被上调。与肝脏炎症，促炎性血浆细胞因子（TNF-α和IL6），结肠次生BA（LCA，DCA）和继发BA产生细菌（例如，与LF组相比，HF组的乳酸杆菌科/ Lachnospiraceae至少高0.5倍。两者合计，数据表明，在进食HF饮食的小鼠中，晚期肝硬变与肝炎，结肠次生胆汁酸及其相关细菌水平升高同时发生。这些数据表明，在晚期肝硬变的阶段可能存在肠道-肝脏串扰。