Abstract

Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.

Maternal obesity predisposes offspring to obesity and metabolic disorders through incompletely understood mechanisms. Here the authors report that Dio3os is an imprinted long-coding RNA that modulates brown adipose tissue development and obesity resistance in the offspring.

Details

Title
Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance
Author
Yan-Ting, Chen 1 ; Qi-Yuan, Yang 1 ; Hu, Yun 1 ; Liu, Xiang-Dong 1 ; de Avila Jeanene M 1   VIAFID ORCID Logo  ; Mei-Jun, Zhu 2 ; Nathanielsz, Peter W 3 ; Du, Min 1   VIAFID ORCID Logo 

1  Washington State University, Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Pullman, USA (GRID:grid.30064.31) (ISNI:0000 0001 2157 6568) 
2  Washington State University, School of Food Sciences, Pullman, USA (GRID:grid.30064.31) (ISNI:0000 0001 2157 6568) 
3  University of Wyoming, Wyoming Pregnancy and Life Course Health Center, Department of Animal Science, Laramie, USA (GRID:grid.135963.b) (ISNI:0000 0001 2109 0381); Texas Biomedical Research Institute, Southwest National Primate Research Center, San Antonio, USA (GRID:grid.250889.e) (ISNI:0000 0001 2215 0219) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-021-27171-1
ProQuest document ID
2602349271
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.