机械加载对高脂饮食诱导的肥胖和非酒精性脂肪肝的治疗作用

目的 探讨机械加载对高脂饮食诱导的肥胖和非酒精性脂肪肝的疗效。方法 选用6周龄的C57BL/6雌性小鼠30只，体质量约18 g，按随机数字表法分为正常对照组（NC组）、高脂饮食组（HF组）和高脂饮食机械加载治疗组（HF+L组），每组10只，持续饮食诱导12周。高脂饮食6周后，HF+L组进行机械加载治疗6周。实验动物进行体成分分析，观测全身体脂含量的变化。收集肾周脂肪、子宫周脂肪、肠系膜脂肪、腹股沟脂肪和肝脏并称量湿质量。留取部分肝脏做组织形态学检测，油红O和HE染色分析观察肝脏的病理改变，部分肝脏用于Western blot检测内质网应激相关蛋白（eIF2α、p-eIF2α、ATF4）的表达。结果 与NC组相比，高脂饮食导致HF组体质量、体脂明显增加，机械加载治疗后，HF+L组体质量、体脂较HF组明显降低（P＜0.05）。肝脏组织学结果表明，高脂饮食导致一定程度的肝脏脂肪变性，通过治疗后，脂肪变性得到有效缓解（P＜0.05）。Western blot分析结果表明，高脂饮食导致小鼠肝脏eIF2α、p-eIF2α和ATF4蛋白表达升高，机械加载能够抑制肝脏p-eIF2α和ATF4蛋白的表达。结论 机械加载能够有效缓解高脂饮食导致的体质量、体脂增加及非酒精性脂肪肝，其治疗作用可能与肝脏内质网应激有关。

The effects of mechanical loading on high-fat induced obesity and non-alcoholic fatty liver disease

Objective To investigate the therapeutic effect of mechanical loading on obesity and non-alcoholic fatty liver disease. Methods Thirty 6-week-old female C57BL/6 mice (body weight 18 g) were randomly assigned into three groups: normal control group (NC group, n=10), high-fat diet group (HF group, n=10) and high-fat diet with mechanical loading treatment group (HF+L group, n=10). All mice except for NC group were fed with high-fat diet for 12 weeks. After 6 weeks of high-fat diet, mice of HF+L group received 6-week mechanical loading. The whole body composition was analyzed to detect the total body fat content. The mesenteric fat, perirenal fat, inguinal fat, periuterine fat and the liver were collected and weighed. A portion of the liver sample was isolated for histological analysis (Oil red O staining and HE staining) to observe pathologic changes, while the other was used for Western blot assay to detect the expression of eIF2α, p-eIF2α and ATF4, which were the marker proteins of endoplasmic reticulum stress. Results Compared with the NC group, high-fat diet resulted in a significant increase in body weight and body fat (P＜0.05). After mechanical loading treatment, the body weight and body fat were significantly decreased in the HF+L group compared with those of HF group (P＜0.05). Hepatic histological analysis showed that high-fat diet induced hepatic steatosis, which was effectively alleviated by mechanical loading treatment (P＜0.05). Western blot analysis indicated that high-fat diet led to higher expression levels of p-eIF2α and ATF4 in liver, and mechanical loading was effective in inhibiting the increased expressions of p-eIF2α and ATF4.Conclusion Mechanical loading can effectively alleviate obesity and non-alcoholic fatty liver disease caused by high-fat diet, and its effects may be associated with endoplasmic reticulum stress in liver