Effects of endoplasmic reticulum stress on adipose tissue in mice

doi:10.3969/j.issn.1000-1565.2022.03.010

Abstract

Abstract: In order to explore the effect of endoplasmic reticulum stress on white adipose tissue in mice, endoplasmic reticulum stress was induced in mice by intraperitoneal injection of tunicamycin.This constructed an endoplasmic reticulum stress mouse model. Then, white fat from the epididymis of mice was obtained. RT-PCR and Western blot were used to detect the mRNA level and protein expression of endoplasmic reticulum stress-related factors in white adipose tissue. The changes of white adipose tissue cells were observed by fluorescence microscope, the content of triglycerides, free fatty acids and the secretion of adipocytokines and inflammatory factors were measured. The results showed that treatment with 1.0 mg/kg tunicamycin for 72 h was the best in inducing endoplasmic reticulum stress in mice. Endoplasmic reticulum stress led to a decrease in the proportion of white adipose tissue, a decrease in fat cell diameter, an increase in lipolysis, a decrease in the secretion of adipocytokines, and an increase in inflammation.- DOI:10.3969/j.issn.1000-1565.2022.03.010内质网应激对小鼠脂肪组织的影响么松慧^1,2,陈慧²,杨洋^2,3,万悦^2,4,初源²,孙磊¹,于淼²(1.河北大学生命科学学院,河北保定 071002;2.军事医学科学院生命组学研究所,北京 100850;3.天津大学化工学院,天津 300072;4.安徽医科大学基础医学院,安徽合肥 230032)摘要:为了探究内质网应激对小鼠白色脂肪组织的影响,通过腹腔注射衣霉素(tunicamycin, TM)诱导小鼠体内内质网应激,构建内质网应激小鼠模型,然后获取小鼠附睾处白色脂肪组织,并采用RT-PCR和Western blot检测白色脂肪组织中内质网应激相关因子的mRNA水平及蛋白表达情况,通过荧光显微镜观察白色脂肪组织细胞的变化,测定甘油三酯、游离脂肪酸含量及脂肪细胞因子和炎症因子分泌情况.结果表明:1.0 mg/kg TM处理72 h诱导小鼠内质网应激效果最佳;内质网应激可以导致白色脂肪组织比例减少,脂肪细胞直径减小,脂解反应增多,脂肪细胞因子分泌减少及炎症反应增多等.该研究结果说明内质网应激可以诱导小鼠脂肪组织中发生脂解,进而介导脂代谢紊乱.关键词:内质网应激;衣霉素;白色脂肪组织;脂代谢中图分类号:Q591.5 文献标志码:A 文章编号:1000-1565(2022)03-0288-07Effects of endoplasmic reticulum stress on adipose tissue in miceYAO Songhui^1,2, CHEN Hui², YANG Yang^2,3, WAN Yue^2,4, CHU Yuan², SUN Lei¹, YU Miao²(1. School of Life Sciences, Hebei University, Baoding 071002, China; 2. Institute of Lifeomics, Academy of Military Medical Sciences, Beijing 100850, China; 3. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; 4. School of Basic Medicine, Anhui Medical University, Hefei 230032, China)Abstract: In order to explore the effect of endoplasmic reticulum stress on white adipose tissue in mice, endoplasmic reticulum stress was induced in mice by intraperitoneal injection of tunicamycin.This constructed an endoplasmic reticulum stress mouse model. Then, white fat from the epididymis of mice was obtained. RT-PCR and Western blot were used to detect the mRNA level and protein expression of endoplasmic reticulum stress-related factors in white adipose tissue. The changes of white adipose tissue cells were observed by fluorescence microscope, the content of triglycerides, free fatty acids and the secretion of adipocytokines and inflammatory factors were measured. The results showed that treatment with 1.0 mg/kg tunicamycin for 72 h was the best in inducing endoplasmic reticulum stress in mice. Endoplasmic reticulum stress led to a decrease in the proportion of white adipose tissue, a decrease in fat cell diameter, an increase in lipolysis, a decrease in the secretion of adipocytokines, and an increase in inflammation.- 收稿日期:2021-12-02 基金项目:国家自然科学基金面上项目(82070596) 第一作者:么松慧(1997—),女,河北唐山人,河北大学在读硕士研究生,主要从事肝脏病理生理研究.E-mail:15703277906@163.com 通信作者:孙磊(1971—),女,河北唐山人,河北大学教授,博士,主要从事环境微生物研究.E-mail:sunlei1018@126.com于淼(1978—),女,浙江湖州人,军事医学科学院副研究员,博士,主要从事肝脏病理生理研究.E-mail:13718674282@163.com第3期么松慧等:内质网应激对小鼠脂肪组织的影响The results of this study indicated that endoplasmic reticulum stress induced lipolysis in mouse adipose tissue, leading to lipid metabolism disorder.

Key words: endoplasmic reticulum stress, tunicamycin, white adipose tissue, lipid metabolism

CLC Number:

Q591.5

YAO Songhui, CHEN Hui, YANG Yang, WAN Yue, CHU Yuan, SUN Lei, YU Miao. Effects of endoplasmic reticulum stress on adipose tissue in mice[J]. Journal of Hebei University(Natural Science Edition), 2022, 42(3): 288-294.

References

[1] BOGDANOVIC E, KRAUS N, PATSOURIS D, et al. Endoplasmic reticulum stress in adipose tissue augments lipolysis[J]. J Cell Mol Med, 2015, 19(1): 82-91. DOI:10.1111/jcmm.12384.
[2] DENG J N, LIU S X, ZOU L Q, et al. Lipolysis response to endoplasmic reticulum stress in adipose cells[J]. J Biol Chem, 2012, 287(9): 6240-6249. DOI:10.1074/jbc.M111.299115.
[3] DEZWAAN-MCCABE D, SHELDON R D, GORECKI M C, et al. ER stress inhibits liver fatty acid oxidation while unmitigated stress leads to anorexia-induced lipolysis and both liver and kidney steatosis[J]. Cell Rep, 2017, 19(9): 1794-1806. DOI:10.1016/j.celrep.2017.05.020.
[4] CHITRAJU C, MEJHERT N, HAAS J T, et al. Triglyceride synthesis by DGAT1 protects adipocytes from lipid-induced ER stress during lipolysis[J]. Cell Metab, 2017, 26(2): 407-418.e3. DOI:10.1016/j.cmet.2017.07.012.
[5] WALTER P, RON D. The unfolded protein response: from stress pathway to homeostatic regulation[J]. Science, 2011, 334(6059): 1081-1086. DOI:10.1126/science.1209038.
[6] SUZUKI T, GAO J H, ISHIGAKI Y, et al. ER stress protein CHOP mediates insulin resistance by modulating adipose tissue macrophage polarity[J]. Cell Rep, 2017, 18(8): 2045-2057. DOI:10.1016/j.celrep.2017.01.076.
[7] 何人可,胡越皓,张嘉平,等.内质网应激在胰岛素抵抗中的作用[J].中国细胞生物学学报, 2016, 38(1): 91-97.
[8] OZCAN U, CAO Q, YILMAZ E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes[J]. Science, 2004, 306(5695): 457-461. DOI:10.1126/science.1103160.
[9] FUCHS C D, CLAUDEL T, KUMARI P, et al. Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice[J]. Hepatology, 2012, 56(1): 270-280. DOI:10.1002/hep.25601.
[10] CHEN Y Q, WU Z H, ZHAO S P, et al. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity[J]. Sci Rep, 2016, 6: 27486. DOI:10.1038/srep27486.
[11] 毛婷,杨柳,刘勇.细胞内质网应激与糖脂代谢紊乱的机制关联[J].中国细胞生物学学报, 2011, 33(7): 727-737.
[12] 孟冉,阮国良,杨代勤.内质网应激与脂类代谢[J].生命科学, 2014, 26(10): 1004-1011. DOI:10.13376/j.cbls/2014144.
[13] 刘江,李伟平,施杰民,等.内质网应激参与细胞脂肪变性的研究[J].医学研究杂志, 2012, 41(12): 122-125. DOI:10.3969/j.issn.1673-548X.2012.12.037.
[14] LUO L, LIU M. Adipose tissue in control of metabolism[J]. J Endocrinol, 2016, 231(3): R77-R99. DOI:10.1530/joe-16-0211.
[15] WANG M, CHEN X, ZHENG Z, et al. Beneficial effect of ER stress preconditioning in protection against FFA-induced adipocyte inflammation via XBP1 in 3T3-L1 adipocytes[J]. Mol Cell Biochem, 2020, 463(1/2): 45-55. DOI:10.1007/s11010-019-03627-3.
[16] ZHOU L, LIU F. Autophagy: roles in obesity-induced ER stress and adiponectin downregulation in adipocytes[J]. Autophagy, 2010, 6(8): 1196-1197. DOI:10.4161/auto.6.8.13478.
[17] 张嵩阳,冯娟,王宪.内质网应激与代谢性心血管疾病: 脂肪因子的作用[J].生理科学进展, 2013, 44(5): 339-344.
[18] PETROVSKI G, DAS S, JUHASZ B, et al. Cardioprotection by endoplasmic reticulum stress-induced autophagy[J]. Antioxid Redox Signal, 2011, 14(11): 2191-2200. DOI:10.1089/ars.2010.3486. (