二甲双胍对高脂饮食诱导的肥胖小鼠肝脏维生素B12的影响及维生素B12与糖脂代谢的关系  

Effect of metformin on liver vitamin B12 in high-fat diet-induced obese mice and relationship between vitamin B12 and glucose and lipid metabolism

作　　者：简颖 郭婉蓉 刘子瑜 梁华 蔡梦茵 许雯 徐芬 JIAN Ying;GUO Wan-rong;LIU Zi-yu;LIANG Hua;CAI Meng-yin;XU Wen;XU Fen(The Third Affiliated Hospital of Sun Yat-sen University,Guangdong Provincial Key Laboratory of Diabetology,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院,广东省糖尿病防治重点实验室,广东广州510630

出　　处：《中国病理生理杂志》2022年第7期1226-1233,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81970741,No.81670782);广东省“珠江人才计划”本土创新科研团队项目资助(No.2017BT01S131);广州市科技计划项目(No.202102010229)。

摘　　要：目的:探讨二甲双胍(Met)对高脂饮食(HFD)喂养的C57BL/6J小鼠血清和肝脏维生素B12水平的影响,以及维生素B12水平的改变与糖脂代谢表型是否相关。方法:将7~8周龄雄性C57BL/6J小鼠用HFD诱导12周构建肥胖小鼠模型,以普通饮食(CD)喂养小鼠作为正常对照组;12周造模成功后再各自随机分为Met(250 mg·kg^(-1)·d^(-1))组和空白对照组干预4周,即总共分为4组,分别为CD组、CD Met组、HFD组和HFD Met组,每组5只。干预过程中检测小鼠的体重和空腹血糖;干预结束后收取标本,分别测定小鼠血清和肝脏中的甘油三酯(TG)、总胆固醇(TC)和维生素B12水平,并对肝组织进行HE和油红O染色。结果:(1)与CD组比较,HFD组小鼠体重、血脂及肝脏TG和TC水平均显著升高,肝脏病理结果显示脂质沉积加重;(2)与HFD组相比,HFD Met组小鼠体重显著下降,肝脏TG和TC水平均显著下降,肝脏病理结果显示脂质沉积改善;(3)4组间的血清维生素B12水平差异无统计学显著性,但HFD Met组肝脏维生素B12水平与CD Met组相比显著下降(P<0.01);(4)维生素B12水平与糖脂代谢各表型的相关性分析显示,血清维生素B12水平与各表型未观察到相关性,而肝脏维生素B12水平与体重、空腹血糖、肝重、血清TG水平、血清TC水平、内脏脂肪重量及皮下脂肪重量均呈负相关(P<0.05)。结论:Met干预HFD诱导的肥胖小鼠可引起肝脏而非血清维生素B12水平的下调,且肝脏维生素B12水平与体重、肝重、血脂水平及空腹血糖等代谢指标呈负相关。AIM:To investigate whether metformin(Met)affects serum and liver vitamin B12 levels in C57BL/6J mice fed with high-fat diet(HFD),and the correlation between vitamin B12 level and metabolic phenotypes.METHODS:Male C57BL/6J mice aged 7 to 8 weeks were fed with HFD for 12 weeks to establish an obese mouse model,and mice fed with chow diet(CD)were used as control group.The mice in each group were further divided into 2 groups:those in one group drunk water with Met at a dose of 250 mg·kg^(-1)·d^(-1)for 4 weeks,and those in the other group drunk normal water as control.Namely the mice were randomly divided into 4 groups:CD group,CD Met group,HFD group and HFD Met group,with 5 mice in each group.During the dietary intervention,body weight and fasting blood glucose were measured.At the end of intervention,the mice were sacrificed and tissues were collected.Triglyceride(TG),total cholesterol(TC)and vitamin B12 levels in serum and liver were measured.Liver HE and oil red O staining were conducted.RESULTS:(1)Compared with CD group,body weight,and serum and liver lipid profiles in HFD group increased significantly,and liver histological observation results showed that lipid deposition was aggravated.(2)Compared with HFD group,body weight,liver TG and liver TC decreased significantly in HFD Met group,and liver histological observation results showed that lipid deposition was alleviated.(3)There was no significant difference in serum vitamin B12 levels among the 4 groups,but liver vitamin B12 levels showed significant reduction in HFD Met group compared with CD Met group(P<0.01).(4)No correlation was observed between the serum vitamin B12 level and metabolic phenotypes.However,liver vitamin B12 level was negatively correlated with body weight,fasting blood glucose,liver weight,serum lipid levels,visceral adipose tissue weight and subcutaneous adipose tissue weight(P<0.05).CONCLUSION:Metformin down-regulates vitamin B12 level in liver rather than in serum when treating the HFD-induced obese mice.The vitamin B12 level in live

关 键 词：二甲双胍 维生素B12 肥胖 糖脂代谢 

分 类 号：R589.9[医药卫生—内分泌] R363.2[医药卫生—内科学]