Aims

The mechanism of physical activity and calorie restriction remedying non-alcoholic fatty liver disease (NAFLD) remains elusive. The purpose of this study is to explore the effects of eccentric exercise and dietary regulation allied or alone on high-fat diet (HFD) induced NAFLD and its potential mechanism.

Materials and methods

Mice were fed with HFD for 12 weeks and subsequently treated with chronic downhill running and caloric restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the liver injury and dyslipidemia. Levels of MCP1, TNFα, IL-1β, IL-6 and IL-10 were detected by ELISA. Liver morphology was observed by H&E and oil red O staining. Protein contents of iNOS, Arg-1, IL-1β and IL-10 were determined by Western blot. CD86 and CD206 fluorescence were determined by Immunofluorescence.

Key finding

(1) 12 weeks' HFD induced hyperlipemia and hepatic steatosis by activating M1 macrophages phenotype and inhibiting M2 macrophages. (2) Chronic downhill running and caloric restriction promoted liver M2 macrophages phenotype, and inhibited M1 macrophages, to attenuate chronic inflammation and ameliorate hepatic steatosis. (3) The effects of downhill running and dietary regulation allied were more effective on improving NAFLD compared with downhill running or caloric restriction alone.

Significance

Eccentric exercise accompanied by caloric restriction attenuates HFD-related NAFLD by promoting M2 macrophages phenotype and inhibiting M1 macrophages in liver. These findings may be help to designing better non-pharmacological intervention programs for NAFLD patients.

中文翻译：

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肝脏巨噬细胞介导下坡跑步和热量限制对高脂饮食喂养小鼠的非酒精性脂肪肝疾病的影响。

目的

纠正非酒精性脂肪性肝病（NAFLD）的身体活动和卡路里限制机制仍然难以捉摸。这项研究的目的是探讨单独或单独进行的离心运动和饮食调节对高脂饮食（HFD）诱导的NAFLD的影响及其潜在机制。

材料和方法

小鼠接受HFD喂养12周，然后接受慢性下坡跑步和热量限制治疗8周。在干预之前和期间检查相关的生化指标，以评估肝损伤和血脂异常。通过ELISA检测MCP1，TNFα，IL-1β，IL-6和IL-10的水平。通过H＆E和油红O染色观察肝形态。通过蛋白质印迹法测定iNOS，Arg-1，IL-1β和IL-10的蛋白质含量。通过免疫荧光测定CD86和CD206荧光。

关键发现

（1）12周的HFD通过激活M1巨噬细胞表型和抑制M2巨噬细胞来诱导高脂血症和肝脂肪变性。（2）慢性下坡跑步和热量限制促进了肝M2巨噬细胞表型，并抑制了M1巨噬细胞，从而减轻了慢性炎症并减轻了肝脂肪变性。（3）与单独下坡跑步或限制热量摄入相比，下坡跑步和饮食调节联合对改善NAFLD的效果更好。

意义

偏心运动伴随热量限制，通过促进肝脏中的M2巨噬细胞表型和抑制M1巨噬细胞来减弱HFD相关的NAFLD。这些发现可能有助于为NAFLD患者设计更好的非药物干预方案。