Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
Reduced Oxidative Stress and Enhanced FGF21 Formation in Livers of Endurance-Exercised Rats with Diet-Induced NASH
复制标题
DOI：
10.3390/nu11112709
复制
发表时间：
2019-11-01
期刊：
影响因子：
5.9
通讯作者：
Pueschel, Gerhard P.
中科院分区：
文献类型：
--
作者：
Henkel, Janin;Buchheim-Dieckow, Katja;Pueschel, Gerhard P.
非酒精性脂肪性肝病（NAFLD）包括严重形式的脂肪性肝炎（NASH）是非常普遍的疾病，没有批准的药物治疗存在。以减肥10%为目标的饮食干预是有效的，但由于依从性低而失败。即使在没有减轻体重的情况下，增加体育活动也是改善NAFLD的一种选择。潜在的机制尚不清楚，无法在人类中进行研究。本研究建立了一个大鼠NAFLD模型，再现了人类饮食诱导的NAFLD的许多方面。在这个模型中研究了耐力运动的影响。雄性Wistar大鼠接受对照食物或富含脂肪、胆固醇和果糖的nash诱导饮食。两个饮食组又被细分为久坐组和耐力运动组。接受NASH诱导饮食的动物体重增加，出现葡萄糖不耐受，并出现脂肪变性、肝细胞肥大、炎症和纤维化等肝脏病理，为NAFLD或NASH的典型症状。与预期相反，耐力运动并没有改善NASH活动评分，甚至加重了肝脏炎症。然而，耐力运动减轻了肝脏胆固醇超载和随之而来的严重氧化应激。此外，运动改善葡萄糖耐量可能部分是通过诱导肝脏FGF21的产生。
Non-alcoholic fatty liver diseases (NAFLD) including the severe form with steatohepatitis (NASH) are highly prevalent ailments to which no approved pharmacological treatment exists. Dietary intervention aiming at 10% weight reduction is efficient but fails due to low compliance. Increase in physical activity is an alternative that improved NAFLD even in the absence of weight reduction. The underlying mechanisms are unclear and cannot be studied in humans. Here, a rat NAFLD model was developed that reproduces many facets of the diet-induced NAFLD in humans. The impact of endurance exercise was studied in this model. Male Wistar rats received control chow or a NASH-inducing diet rich in fat, cholesterol, and fructose. Both diet groups were subdivided into a sedentary and an endurance exercise group. Animals receiving the NASH-inducing diet gained more body weight, got glucose intolerant and developed a liver pathology with steatosis, hepatocyte hypertrophy, inflammation and fibrosis typical of NAFLD or NASH. Contrary to expectations, endurance exercise did not improve the NASH activity score and even enhanced hepatic inflammation. However, endurance exercise attenuated the hepatic cholesterol overload and the ensuing severe oxidative stress. In addition, exercise improved glucose tolerance possibly in part by induction of hepatic FGF21 production.