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author Huang, Zhengyun
Liu, Xiangpeng
Chen, Xiyue
Zhou, You
Chen, Qian
Liu, Yan
Zhu, Hongyun
Cheng, Ken
Feng, Yu
Dong, Miren
Song, Linsheng
Wang, Lingling
Liu, Shiqi
Shan, Tizhong
Kuang, Shihuan
Dong, Yingying
Vidal-Puig, Antonio
Zhang, Yong
Jia, Zhihao
author_facet Huang, Zhengyun
Liu, Xiangpeng
Chen, Xiyue
Zhou, You
Chen, Qian
Liu, Yan
Zhu, Hongyun
Cheng, Ken
Feng, Yu
Dong, Miren
Song, Linsheng
Wang, Lingling
Liu, Shiqi
Shan, Tizhong
Kuang, Shihuan
Dong, Yingying
Vidal-Puig, Antonio
Zhang, Yong
Jia, Zhihao
Huang, Zhengyun
Liu, Xiangpeng
Chen, Xiyue
Zhou, You
Chen, Qian
Liu, Yan
Zhu, Hongyun
Cheng, Ken
Feng, Yu
Dong, Miren
Song, Linsheng
Wang, Lingling
Liu, Shiqi
Shan, Tizhong
Kuang, Shihuan
Dong, Yingying
Vidal-Puig, Antonio
Zhang, Yong
Jia, Zhihao
collection PubMed - marine biology
contents PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility. Huang, Zhengyun Liu, Xiangpeng Chen, Xiyue Zhou, You Chen, Qian Liu, Yan Zhu, Hongyun Cheng, Ken Feng, Yu Dong, Miren Song, Linsheng Wang, Lingling Liu, Shiqi Shan, Tizhong Kuang, Shihuan Dong, Yingying Vidal-Puig, Antonio Zhang, Yong Jia, Zhihao Animals Protein-Arginine N-Methyltransferases Male Mice Arginine Fasting Obesity Intermittent Fasting Insulin Mice, Inbred C57BL Methylation Adipocytes Protein Processing, Post-Translational Insulin Resistance Signal Transduction Humans Mice, Knockout Adaptation, Physiological Diet, High-Fat Obesity impairs metabolic flexibility-the capacity to adapt to fluctuating energy demands. Emerging evidence suggests that dietary interventions, particularly time-restricted feeding (TRF), may help restore this flexibility. In this study, we demonstrate that feeding upregulates PRMT3 and asymmetric dimethylarginine (ADMA)-containing proteins via insulin-pAKT signaling, while fasting reduces their expression. Pharmacological inhibition of PRMT3 attenuates diet-induced obesity (DIO) and enhances adipocyte glycolysis in male mice. Mechanistically, PRMT3 drives the expression of citrate transporter SLC25A1 during feeding through direct arginine methylation. A 16:8 TRF regimen normalizes PRMT3 and ADMA levels while suppressing SLC25A1 expression. Notably, PRMT3 inhibition recapitulates the metabolic benefits of 16:8 TRF and improves metabolic flexibility. Furthermore, adipocyte-specific deletion of Slc25a1 in male mice protects against DIO and enhances insulin sensitivity. Collectively, these findings identify PRMT3-mediated arginine methylation in vWAT as a nutrient-responsive regulatory axis that impairs metabolic flexibility in obesity, which is a potential therapeutic target.
format Artículo científico
id pubmed_41629293
institution PubMed
language en
publishDate 2026
publisher Nature communications
record_format pubmed
spellingShingle PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility.
Huang, Zhengyun
Liu, Xiangpeng
Chen, Xiyue
Zhou, You
Chen, Qian
Liu, Yan
Zhu, Hongyun
Cheng, Ken
Feng, Yu
Dong, Miren
Song, Linsheng
Wang, Lingling
Liu, Shiqi
Shan, Tizhong
Kuang, Shihuan
Dong, Yingying
Vidal-Puig, Antonio
Zhang, Yong
Jia, Zhihao
Animals
Protein-Arginine N-Methyltransferases
Male
Mice
Arginine
Fasting
Obesity
Intermittent Fasting
Insulin
Mice, Inbred C57BL
Methylation
Adipocytes
Protein Processing, Post-Translational
Insulin Resistance
Signal Transduction
Humans
Mice, Knockout
Adaptation, Physiological
Diet, High-Fat
PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility. Huang, Zhengyun Liu, Xiangpeng Chen, Xiyue Zhou, You Chen, Qian Liu, Yan Zhu, Hongyun Cheng, Ken Feng, Yu Dong, Miren Song, Linsheng Wang, Lingling Liu, Shiqi Shan, Tizhong Kuang, Shihuan Dong, Yingying Vidal-Puig, Antonio Zhang, Yong Jia, Zhihao Animals Protein-Arginine N-Methyltransferases Male Mice Arginine Fasting Obesity Intermittent Fasting Insulin Mice, Inbred C57BL Methylation Adipocytes Protein Processing, Post-Translational Insulin Resistance Signal Transduction Humans Mice, Knockout Adaptation, Physiological Diet, High-Fat Obesity impairs metabolic flexibility-the capacity to adapt to fluctuating energy demands. Emerging evidence suggests that dietary interventions, particularly time-restricted feeding (TRF), may help restore this flexibility. In this study, we demonstrate that feeding upregulates PRMT3 and asymmetric dimethylarginine (ADMA)-containing proteins via insulin-pAKT signaling, while fasting reduces their expression. Pharmacological inhibition of PRMT3 attenuates diet-induced obesity (DIO) and enhances adipocyte glycolysis in male mice. Mechanistically, PRMT3 drives the expression of citrate transporter SLC25A1 during feeding through direct arginine methylation. A 16:8 TRF regimen normalizes PRMT3 and ADMA levels while suppressing SLC25A1 expression. Notably, PRMT3 inhibition recapitulates the metabolic benefits of 16:8 TRF and improves metabolic flexibility. Furthermore, adipocyte-specific deletion of Slc25a1 in male mice protects against DIO and enhances insulin sensitivity. Collectively, these findings identify PRMT3-mediated arginine methylation in vWAT as a nutrient-responsive regulatory axis that impairs metabolic flexibility in obesity, which is a potential therapeutic target.
title PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility.
topic Animals
Protein-Arginine N-Methyltransferases
Male
Mice
Arginine
Fasting
Obesity
Intermittent Fasting
Insulin
Mice, Inbred C57BL
Methylation
Adipocytes
Protein Processing, Post-Translational
Insulin Resistance
Signal Transduction
Humans
Mice, Knockout
Adaptation, Physiological
Diet, High-Fat
url https://pubmed.ncbi.nlm.nih.gov/41629293/