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The Association of Fructose Metabolism With Anesthesia/Surgery-Induced Lactate Production
Lei Zhang1,2, Jianhui Liu3, Zhengjie Miao1
1From the Department of Anesthesiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Surgery and anesthesia can increase brain lactate, leading to cognitive impairment in elderly patients. This study reveals that fructose metabolism drives this lactate increase, suggesting it as a therapeutic target for preventing delayed neurocognitive recovery.
Area of Science:
- Neuroscience
- Metabolic Research
- Geriatric Medicine
Background:
- Postoperative cognitive impairment, including delayed neurocognitive recovery (dNCR), is a concern in elderly individuals.
- Excessive brain lactate levels are implicated in dNCR, but their origin remains unclear.
Purpose of the Study:
- To investigate the association between metabolic pathways and the development of postoperative dNCR.
- To identify the source of increased brain lactate following anesthesia and surgery.
Main Methods:
- Studied 43 elderly patients undergoing surgery and a mouse model of postoperative dNCR.
- Utilized metabolomics, isotope labeling, and metabolic flux analysis to track metabolites and metabolic pathways.
- Assessed cognitive function using Barnes maze and Y maze tests in mice.
Main Results:
- Patients and mice developing dNCR showed significantly decreased levels of fructose 1-phosphate.
- Fructose, not glucose, entered glycolysis post-anesthesia/surgery, increasing brain lactate levels in mice.
- Inhibiting fructose metabolism reduced brain lactate and improved cognitive function in mice.
Conclusions:
- Anesthesia and surgery activate fructose metabolism, leading to excessive brain lactate and associated cognitive impairment.
- Targeting fructose metabolism presents a potential therapeutic strategy for mitigating dNCR.
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