Cigarette Smoking Exacerbates Nonalcoholic Fatty Liver Disease in Obese Rats
Cigarette Smoking Exacerbates Nonalcoholic Fatty Liver Disease in Obese Rats
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DOI：
10.1002/hep.23516
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发表时间：
2010-05-01
期刊：
影响因子：
13.5
通讯作者：
Bataller, Ramon
中科院分区：
文献类型：
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作者：
Azzalini, Lorenzo;Ferrer, Elisabet;Bataller, Ramon
吸烟（CS）的患病率在肥胖受试者中增加，这些受试者易患非酒精性脂肪性肝病（NAFLD）。我们研究了CS在对照和肥胖大鼠中的肝脏作用。将对照和肥胖Zucker大鼠分为吸烟者和非吸烟者（每组n = 12）。吸烟大鼠每天吸烟2支，每周5天，持续4周。通过生化分析、肝组织学检查、免疫组化和基因表达分析来评估CS的作用。通过蛋白质印迹法评估AKT和细胞外信号调节激酶（ERK）的磷酸化和羰基化蛋白的定量。正如预期的那样，肥胖大鼠表现出高胆固醇血症、胰岛素抵抗和NAFLD的组织学特征。吸烟并没有改变血糖或葡萄糖的血清配置文件。吸烟增加丙氨酸氨基转移酶血清水平和肥胖大鼠肝损伤的程度，而它只引起对照组大鼠的微小变化。重要的是，CS增加了肥胖大鼠NAFLD的组织学严重程度。我们还探讨了CS有害作用的潜在机制。吸烟增加了肥胖大鼠的氧化应激和肝细胞凋亡的程度，但在对照组中没有。类似地，吸烟增加了肥胖大鼠肝脏中金属蛋白酶组织抑制剂-1和1型胶原蛋白原的表达，但在对照组中没有。最后，吸烟调节ERK和AKT磷酸化。CS的有害影响，没有观察到短期暴露后（5天）。结论：CS可引起肥胖大鼠氧化应激，加重NAFLD的严重程度。进一步的研究应该评估这一发现是否也发生在肥胖和NAFLD患者中。（《肝脏学》2010年;51：1567-1576）
The prevalence of cigarette smoking (CS) is increased among obese subjects, who are susceptible to develop nonalcoholic fatty liver disease (NAFLD). We investigated the hepatic effects of CS in control and obese rats. Control and obese Zucker rats were divided into smokers and nonsmokers (n = 12 per group). Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. The effects of CS were assessed by biochemical analysis, hepatic histological examination, immunohistochemistry, and gene expression analysis. Phosphorylation of AKT and extracellular signal-regulated kinase (ERK) and quantification of carbonylated proteins were assessed by western blotting. As expected, obese rats showed hypercholesterolemia, insulin resistance, and histological features of NAFLD. Smoking did not modify the lipidic or glucidic serum profiles. Smoking increased alanine aminotransferase serum levels and the degree of liver injury in obese rats, whereas it only induced minor changes in control rats. Importantly, CS increased the histological severity of NAFLD in obese rats. We also explored the potential mechanisms involved in the deleterious effects of CS. Smoking increased the degree of oxidative stress and hepatocellular apoptosis in obese rats, but not in controls. Similarly, smoking increased the hepatic expression of tissue inhibitor of metalloproteinase-1 and procollagen-alpha2(I) in obese rats, but not in controls. Finally, smoking regulated ERK and AKT phosphorylation. The deleterious effects of CS were not observed after a short exposure (5 days). Conclusion: CS causes oxidative stress and worsens the severity of NAFLD in obese rats. Further studies should assess whether this finding also occurs in patients with obesity and NAFLD. (HEPATOLOGY 2010;51:1567-1576.)