Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue

作者：Danqing Yu, Pingping Lv, Yi‐Shang Yan, Guanxin Xu, Annapurna Sadhukhan, Shan Dong, Yan Shen, Jun Ren, Xueying Zhang, Chun Feng, Yiting Huang, Shen Tian, Yin Zhou, Yiting Cai, Zhenhua Ming, Guolian Ding, Hong Zhu, Jian‐Zhong Sheng, Min Jin, He‐Feng Huang · 发表于：The FASEB Journal · 年份：2019 · DOI：10.1096/fj.201801818r · 被引用次数：50 · 研究领域：Adipose Tissue and Metabolism、Birth, Development, and Health、Fatty Acid Research and Health

ABSTRACT 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 [ 18 F]‐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...