Premium
Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue
Author(s) -
Yu DanQing,
Lv PingPing,
Yan YiShang,
Xu GuanXin,
Sadhukhan Annapurna,
Dong Shan,
Shen Yan,
Ren Jun,
Zhang XueYing,
Feng Chun,
Huang YiTing,
Tian Shen,
Zhou Yin,
Cai YiTing,
Ming ZhenHua,
Ding GuoLian,
Zhu Hong,
Sheng JianZhong,
Jin Min,
Huang HeFeng
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801818r
Subject(s) - brown adipose tissue , adipose tissue , endocrinology , medicine , physiology
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 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