目的 探讨锰（manganese,Mn）补充对高脂饮食诱导小鼠肥胖的改善作用。方法 48只雄性C57BL/6小鼠随机分为4组,即对照（control）组、锰（Mn）组、肥胖（HFD）组、肥胖Mn补充（HFD+Mn）组,每组12只;HFD组和HFD+Mn组小鼠给予高脂饲料喂养,Control和Mn组给予对照饲料喂养,共12 w,Mn和HFD+Mn组分别在对照饮食和高脂饮食期间给与小鼠1.43 mg/kg的Mn;记录小鼠体重变化,测量体脂率;12 w后处死小鼠,采集血液和组织标本,测定血锰含量及血清生化指标,观察棕色脂肪组织（brown adipose tissue,BAT）病理学变化,通过分析BAT活性氧（reactive oxygen species,ROS）和丙二醛（malondialdehyde,MDA）含量评价小鼠BAT氧化应激情况,通过检测BAT线粒体活性氧（mitochondrial reactive oxygen species,mtROS）、ATP水平以及线粒体膜电位评估Mn补充和高脂饮食对小鼠BAT线粒体功能的影响。结果 与对照组相比,HFD组小鼠体重和体脂明显增加（P<0.05）;血清总胆固醇（total cholesterol,TC）、甘油三酯（triglyceride,TG）、低密度脂蛋白（low-density lipoprotein cholesterol,LDL-C）显著升高,高密度脂蛋白（high-density lipoprotein cholesterol,HDL-C）明显降低（P<0.05）;HE染色提示BAT组织形态异常, ROS和MDA含量增加（P<0.05）, mtROS水平升高、ATP含量以及线粒体膜电位降低（P<0.05）; Mn补充明显减轻肥胖小鼠体重和体脂（P<0.05）,改善血脂水平异常（P<0.05）以及BAT形态异常,减轻BAT氧化应激和线粒体功能损伤（P<0.05）。结论 Mn补充可改善高脂饮食诱导的小鼠肥胖,其机制可能与调控BAT线粒体功能有关。
Abstract
Objective To investigate the effects of manganese supplementation on the obesity induced by high-fat diet in mice. Methods Forty-eight male C57BL/6 mice were randomly divided into four groups: control group (control), manganese group (Mn), high-fat diet group (HFD), and HFD plus manganese supplementation group (HFD+Mn), with 12 mice in each group. Groups HFD and HFD+Mn were fed a high-fat diet (60% fat, 20% protein and 20% carbohydrate) for 12 weeks, and the other two groups were fed a control diet (10% fat, 20% protein and 70% carbohydrate). The Mn and the HFD+Mn groups were received 1.43 mg/kg Mn orally during the feeding period. Body weight and body composition were detected. After 12 weeks, the mice were anesthesized and specimens were collected. The contents of manganese in blood and biochemical markers in serum were examined. The pathological change of brown adipose tissue (BAT) was observed. The oxidative stress were evaluated in brown adipose tissue (BAT) by analyzing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). The effects of Mn supplementation and HFD on BAT mitochondrial function were assessed by detecting the mitochondrial ROS (mtROS), ATP level and mitochondrial membrane potential. Results Compared to the control group, body weight, fat mass, and serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) of the HFD group were notably elevated (P<0.05), while the level of high-density lipoprotein cholesterol (HDL-C) significantly reduced (P<0.05). HE staining revealed that the morphology of BAT was abnormal in the HFD group. The oxidative stress in BAT was obviously increased, manifested as increased contents of ROS and MDA. Increase of mitochondrial ROS (mtROS), and decrease of ATP level and mitochondrial membrane potential were also observed in BAT (P<0.05). Mn supplementation reduced the degree of obesity in mice (P<0.05), improved serum lipid levels (P<0.05), and alleviated the abnormal morphology of BAT. Mn supplementation also decreased oxidative stress and improved mitochondrial function in BAT (P<0.05). Conclusion Mn supplementation can ameliorate obesity induced by high-fat diet and improve mitochondrial function of BAT in mice.
关键词
肥胖 /
锰 /
棕色脂肪 /
线粒体功能 /
小鼠
Key words
obesity /
manganese /
brown adipose tissue /
mitochondrial function /
mice
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基金
辽宁省教育厅基本科研项目（No. LJ212410160066）; 锦州医科大学大学生创新创业训练计划项目（No. X202510160061）
