Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling
Summary: In mammals, maternal obesity typically impairs brown adipose tissue (BAT) formation in fetuses, increasing their risk of metabolic disorders in adulthood. However, the mechanisms behind this phenomenon are not well understood. Our single-nucleus transcriptomic analysis revealed dynamic chan...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725007065 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839646116571774976 |
|---|---|
| author | Lun Hua Wenxue Shen Dengfeng Gao Yi Yang Xiaohan Yang Haoqi Zhang Siyuan Liu Luting Liu Yaxue Cao Xuemei Jiang Xingfa Han Chao Jin Bin Feng Lianqiang Che Shengyu Xu Yan Lin Jian Li Zhengfeng Fang Ting Luo Mingzhou Li De Wu Yong Zhuo |
| author_facet | Lun Hua Wenxue Shen Dengfeng Gao Yi Yang Xiaohan Yang Haoqi Zhang Siyuan Liu Luting Liu Yaxue Cao Xuemei Jiang Xingfa Han Chao Jin Bin Feng Lianqiang Che Shengyu Xu Yan Lin Jian Li Zhengfeng Fang Ting Luo Mingzhou Li De Wu Yong Zhuo |
| author_sort | Lun Hua |
| collection | DOAJ |
| description | Summary: In mammals, maternal obesity typically impairs brown adipose tissue (BAT) formation in fetuses, increasing their risk of metabolic disorders in adulthood. However, the mechanisms behind this phenomenon are not well understood. Our single-nucleus transcriptomic analysis revealed dynamic changes in cell heterogeneity within the fetal interscapular BAT (iBAT) from obese dams, leading to compromised thermogenesis in their offspring. Obese dams displayed elevated levels of circulating fibroblast growth factor 21 (FGF21), while their fetuses exhibited lower circulating FGF21 due to reduced trans-placental transfer. Maternal FGF21, significantly increased during late gestation, was the primary source of fetal FGF21, played a crucial role in regulating fetal brown adipogenesis, and likely prevented metabolic dysfunction in offspring. Additionally, the impaired iBAT development in utero due to maternal obesity could be mitigated by postnatal FGF21 supplementation. This study suggests that FGF21 signaling is a promising target for addressing impaired BAT development in fetuses resulting from maternal obesity. |
| format | Article |
| id | doaj-art-f59c0baec5c84a31a07ab6eaf8cfbbe2 |
| institution | Matheson Library |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-f59c0baec5c84a31a07ab6eaf8cfbbe22025-07-01T04:09:14ZengElsevierCell Reports2211-12472025-07-01447115935Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signalingLun Hua0Wenxue Shen1Dengfeng Gao2Yi Yang3Xiaohan Yang4Haoqi Zhang5Siyuan Liu6Luting Liu7Yaxue Cao8Xuemei Jiang9Xingfa Han10Chao Jin11Bin Feng12Lianqiang Che13Shengyu Xu14Yan Lin15Jian Li16Zhengfeng Fang17Ting Luo18Mingzhou Li19De Wu20Yong Zhuo21Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaSchool of Life Sciences, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China; Corresponding authorState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Corresponding authorAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Corresponding authorAnimal Nutrition Institute, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, China; Corresponding authorSummary: In mammals, maternal obesity typically impairs brown adipose tissue (BAT) formation in fetuses, increasing their risk of metabolic disorders in adulthood. However, the mechanisms behind this phenomenon are not well understood. Our single-nucleus transcriptomic analysis revealed dynamic changes in cell heterogeneity within the fetal interscapular BAT (iBAT) from obese dams, leading to compromised thermogenesis in their offspring. Obese dams displayed elevated levels of circulating fibroblast growth factor 21 (FGF21), while their fetuses exhibited lower circulating FGF21 due to reduced trans-placental transfer. Maternal FGF21, significantly increased during late gestation, was the primary source of fetal FGF21, played a crucial role in regulating fetal brown adipogenesis, and likely prevented metabolic dysfunction in offspring. Additionally, the impaired iBAT development in utero due to maternal obesity could be mitigated by postnatal FGF21 supplementation. This study suggests that FGF21 signaling is a promising target for addressing impaired BAT development in fetuses resulting from maternal obesity.http://www.sciencedirect.com/science/article/pii/S2211124725007065CP: Metabolism |
| spellingShingle | Lun Hua Wenxue Shen Dengfeng Gao Yi Yang Xiaohan Yang Haoqi Zhang Siyuan Liu Luting Liu Yaxue Cao Xuemei Jiang Xingfa Han Chao Jin Bin Feng Lianqiang Che Shengyu Xu Yan Lin Jian Li Zhengfeng Fang Ting Luo Mingzhou Li De Wu Yong Zhuo Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling Cell Reports CP: Metabolism |
| title | Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling |
| title_full | Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling |
| title_fullStr | Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling |
| title_full_unstemmed | Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling |
| title_short | Maternal obesity impairs fetal brown adipogenesis by attenuating fetal FGF21 signaling |
| title_sort | maternal obesity impairs fetal brown adipogenesis by attenuating fetal fgf21 signaling |
| topic | CP: Metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725007065 |
| work_keys_str_mv | AT lunhua maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT wenxueshen maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT dengfenggao maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT yiyang maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT xiaohanyang maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT haoqizhang maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT siyuanliu maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT lutingliu maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT yaxuecao maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT xuemeijiang maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT xingfahan maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT chaojin maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT binfeng maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT lianqiangche maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT shengyuxu maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT yanlin maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT jianli maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT zhengfengfang maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT tingluo maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT mingzhouli maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT dewu maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling AT yongzhuo maternalobesityimpairsfetalbrownadipogenesisbyattenuatingfetalfgf21signaling |