TY - JOUR
T1 - A metabolome atlas of mouse brain on the global metabolic signature dynamics following short-term fasting
AU - Shao, Yaping
AU - Fu, Zhenfa
AU - Wang, Yanfeng
AU - Yang, Zhaofei
AU - Lin, Yushan
AU - Li, Song
AU - Cheng, Cheng
AU - Wei, Min
AU - Liu, Zheyi
AU - Xu, Guowang
AU - Le, Weidong
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (NSFC 22004013, 82271524, and 21934006), Doctoral Scientific Research Foundation of the Liaoning Science and Technology Department (2020-BS-200), and the Central Guidance on Local Science and Technology Development Fund of Dalian Science and Technology Bureau.
Publisher Copyright:
© 2023, West China Hospital, Sichuan University.
PY - 2023/12
Y1 - 2023/12
N2 - Calorie restriction (CR) or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders, ameliorate autoimmune diseases, and attenuate aging. Despite efforts, the mechanisms by which CR improves health, particularly brain health, are still not fully understood. Metabolic homeostasis is vital for brain function, and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions. Herein, we applied gas chromatography-mass spectrometry-based metabolomics and lipidomics, covering 797 structurally annotated metabolites, to investigate the metabolome of seven brain regions in fasted (3, 6, 12, and 24 h) and ad libitum fed mice. Using multivariate and univariate statistical techniques, we generated a metabolome atlas of mouse brain on the global metabolic signature dynamics across multiple brain regions following short-term fasting (STF). Significant metabolic differences across brain regions along with STF-triggered region-dependent metabolic remodeling were identified. We found that STF elicited triacylglycerol degradation and lipolysis to compensate for energy demand under fasting conditions. Besides, changes in amino acid profiles were observed, which may play crucial roles in the regulation of energy metabolism, neurotransmitter signaling, and anti-inflammatory and antioxidant in response to STF. Additionally, this study reported, for the first time, that STF triggers a significant elevation of N-acylethanolamines, a class of neuroprotective lipids, in the brain and liver. These findings provide novel insights into the molecular basis and mechanisms of CR and offer a comprehensive resource for further investigation.
AB - Calorie restriction (CR) or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders, ameliorate autoimmune diseases, and attenuate aging. Despite efforts, the mechanisms by which CR improves health, particularly brain health, are still not fully understood. Metabolic homeostasis is vital for brain function, and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions. Herein, we applied gas chromatography-mass spectrometry-based metabolomics and lipidomics, covering 797 structurally annotated metabolites, to investigate the metabolome of seven brain regions in fasted (3, 6, 12, and 24 h) and ad libitum fed mice. Using multivariate and univariate statistical techniques, we generated a metabolome atlas of mouse brain on the global metabolic signature dynamics across multiple brain regions following short-term fasting (STF). Significant metabolic differences across brain regions along with STF-triggered region-dependent metabolic remodeling were identified. We found that STF elicited triacylglycerol degradation and lipolysis to compensate for energy demand under fasting conditions. Besides, changes in amino acid profiles were observed, which may play crucial roles in the regulation of energy metabolism, neurotransmitter signaling, and anti-inflammatory and antioxidant in response to STF. Additionally, this study reported, for the first time, that STF triggers a significant elevation of N-acylethanolamines, a class of neuroprotective lipids, in the brain and liver. These findings provide novel insights into the molecular basis and mechanisms of CR and offer a comprehensive resource for further investigation.
UR - http://www.scopus.com/inward/record.url?scp=85170191875&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85170191875&partnerID=8YFLogxK
U2 - 10.1038/s41392-023-01552-y
DO - 10.1038/s41392-023-01552-y
M3 - Article
C2 - 37679319
AN - SCOPUS:85170191875
SN - 2095-9907
VL - 8
JO - Signal Transduction and Targeted Therapy
JF - Signal Transduction and Targeted Therapy
IS - 1
M1 - 334
ER -