Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue
Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue
复制标题
宫内暴露于高血糖会阻碍棕色脂肪组织的发育
DOI：
10.1096/fj.201801818r
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发表时间：
2019-04-01
期刊：
影响因子：
4.8
通讯作者：
Huang，He-Feng
中科院分区：
文献类型：
--
作者：
Yu，Dan-Qing;Lv，Ping-Ping;Huang，He-Feng
褐色脂肪组织（BAT）是一种独特的非寒颤产热组织。它以脂质和葡萄糖为燃料，参与能量和代谢稳态。妊娠期糖尿病期间宫内暴露于高血糖可导致胎儿发育和成年期代谢表型异常。然而，宫内高血糖是否影响BAT的发展尚不清楚。在本研究中，通过在妊娠小鼠交媾后1d注射链脲佐菌素，将小鼠胚胎暴露于宫内高血糖环境中。采用苏木精染色、伊红染色及免疫组化分析检测BAT的结构。采用[18F] -氟- 2 -脱氧葡萄糖-微正电子发射断层扫描法测定体内BAT的葡萄糖摄取。采用real - time PCR检测BAT中的基因表达，并定量分析5 ‘ - C - phosphate - G - 3 ’位点特异性甲基化。宫内高血糖暴露导致成年期BAT结构受损和BAT葡萄糖摄取功能下降。在出生后18.5天和16周龄时宫内高血糖暴露导致BAT中参与产热和线粒体呼吸链的基因，如Ucp1、Cox5b和Elovl3的表达下调。此外，在链脲佐菌素诱导的糖尿病母亲的后代中，发现Ucp1、Cox5b和Elovl3的甲基化水平较高。我们的研究结果为宫内高血糖对后代BAT发育的持久抑制作用提供了证据。宫内高血糖与后代BAT特异性基因的DNA甲基化增加有关，这支持表观遗传参与。yu, d .问。， P. - P.；王志强，杨毅。，徐，G. - X。张晓宇，任建军，张晓宇，张晓宇。，冯超，黄玉涛。周勇，蔡玉涛，周玉涛，田世祥。，明，z - H。丁志强，刘志强。朱辉，盛建忠，陈建明。，金敏，黄洪峰，黄洪峰。宫内暴露于高血糖会延缓棕色脂肪组织的发育。中国生物医学工程学报，2016,33(2):559 - 559（2019）。www.fasebj.org
Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc). The structure of BAT was examined by hematoxylin and eosin staining and immunohistochemical analysis. The glucose uptake in BAT was measured in vivo by [18F]‐fluoro‐2‐deoxyglucose–micro–positron emission tomography. The gene expression in BAT was determined by real‐time PCR, and the 5′‐C‐phosphate‐G‐3′ site‐specific methylation was quantitatively analyzed. Intrauterine hyperglycemia exposure resulted in the impaired structure of BAT and decreased glucose uptake function in BAT in adulthood. The expressions of the genes involved in thermogenesis and mitochondrial respiratory chain in BAT, such as Ucp1, Cox5b, and Elovl3, were down‐regulated by intrauterine hyperglycemia exposure at 18.5 dpc and at 16 wk of age. Furthermore, higher methylation levels of Ucp1, Cox5b, and Elovl3 were found in offspring of mothers with streptozotocin‐induced diabetes. Our results provide the evidence for enduring inhibitory effects of intrauterine hyperglycemia on BAT development in offspring. Intrauterine hyperglycemia is associated with increased DNA methylation of the BAT specific genes in offspring, which support an epigenetic involvement.—Yu, D.‐Q., Lv, P.‐P., Yan, Y.‐S., Xu, G.‐X., Sadhukhan, A., Dong, S., Shen, Y., Ren, J., Zhang, X.‐Y., Feng, C., Huang, Y.‐T., Tian, S., Zhou, Y., Cai, Y.‐T., Ming, Z.‐H., Ding, G.‐L., Zhu, H., Sheng, J.‐Z., Jin, M., Huang, H.‐F. Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue. FASEB J. 33, 5425–5439 (2019). www.fasebj.org