来自杂志 Cell metabolism 的文献。
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1.
小W
(2023-06-30 23:48):
#paper doi：https://doi.org/10.1016/j.cmet.2023.05.008 Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia 一项关于生酮饮食（KD）饿死肿瘤的研究。之前的研究（2022）指出生酮饮食的代谢产物β-羟丁酸（BHB，脂肪酸代谢后产生的酮体）可通过与细胞表面受体Hcar2结合，诱导转录调节因子Hopx表达增加，从而抑制肿瘤细胞增殖。本文则发现在产生IL-6相关（肝脏生酮损伤）的癌症小鼠模型，生酮饮食的抗癌作用与存活率（OS）不符合。生酮饮食延缓小鼠的肿瘤生长，但加速恶病质的进展，导致总体生存期缩短。作者通过代谢组学和转录组学数据，证明在肿瘤中，KD不仅通过营养剥夺，同时脂质过氧化增加，导致癌细胞的铁死亡。在宿主系统中KD增加了脂质氢过氧化物（looh）的产生，使GSH通路饱和，消耗NADPH储存，同时导致LPPs的积累，导致应激引起的食欲抑制因子GDF-15的升高。NADPH辅助因子的不足，导致下丘脑-垂体-肾上腺（HPA）轴缺陷，诱导相对低皮质酮血症，导致应激反应缺陷和癌症恶病质的早期发作。地塞米松（皮质类固醇）给药，降低了正常饮食喂养小鼠的PFS和OS，延长了KD喂养小鼠的PFS和OS。IL-6相关癌症小鼠OS：KD / 正常 + 地塞米松 < 正常 < KD + 地塞米松。IL-6相关癌症小鼠PFS：正常 + 地塞米松 < 正常 < KD / KD + 地塞米松。
Abstract:
Glucose dependency of cancer cells can be targeted with a high-fat, low-carbohydrate ketogenic diet (KD). However, in IL-6-producing cancers, suppression of the hepatic ketogenic potential hinders the utilization of KD …
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Glucose dependency of cancer cells can be targeted with a high-fat, low-carbohydrate ketogenic diet (KD). However, in IL-6-producing cancers, suppression of the hepatic ketogenic potential hinders the utilization of KD as energy for the organism. In IL-6-associated murine models of cancer cachexia, we describe delayed tumor growth but accelerated cachexia onset and shortened survival in mice fed KD. Mechanistically, this uncoupling is a consequence of the biochemical interaction of two NADPH-dependent pathways. Within the tumor, increased lipid peroxidation and, consequently, saturation of the glutathione (GSH) system lead to the ferroptotic death of cancer cells. Systemically, redox imbalance and NADPH depletion impair corticosterone biosynthesis. Administration of dexamethasone, a potent glucocorticoid, increases food intake, normalizes glucose levels and utilization of nutritional substrates, delays cachexia onset, and extends the survival of tumor-bearing mice fed KD while preserving reduced tumor growth. Our study emphasizes the need to investigate the effects of systemic interventions on both the tumor and the host to accurately assess therapeutic potential. These findings may be relevant to clinical research efforts that investigate nutritional interventions such as KD in patients with cancer.
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2.
哪有情可长
(2023-02-28 20:25):
#paper Atlas of exercise metabolism reveals timedependent signatures of metabolic homeostasis，Cell Metabolism,15 January 2022, doi.org/10.1016/j.cmet.2021.12.016. 组织对运动的敏感性和反应会因为运动时间和生物钟的调整而不同，目前什么时间运动能够引发理想代谢结果还没有完全确定。作者为了解决组织如何独立和协调的对定时运动做出反应，利用7种小鼠组织和血清在一天不同的时间点进行急性运动后鉴定起代谢物的反应。通过对不同组织之间代谢物的动力学比较分析，揭示了一天中特定时间运动的局部和全身代谢物的无差异。通过构建运动代谢图谱，发现了跟跟时间依赖性运动代谢产物2-HB的产生和分布的清晰和生理背景，说明了运动对代谢的健康有促进作用。另外该作者在2018年，cell上也发表了一篇生物钟相关的文章：Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks。作者同时对8个小鼠组织进行了24小时代谢组学分析。在系统能量平衡和慢性营养应激(高脂饮食[HFD])的背景下，展示了昼夜节律代谢的时空图谱。
Abstract:
Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is …
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Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day. Comparative analyses of intra- and inter-tissue metabolite dynamics, including temporal profiling and blood sampling across liver and hindlimb muscles, uncovered an unbiased view of local and systemic metabolic responses to exercise unique to time of day. This comprehensive atlas of exercise metabolism provides clarity and physiological context regarding the production and distribution of canonical and novel time-dependent exerkine metabolites, such as 2-hydroxybutyrate (2-HB), and reveals insight into the health-promoting benefits of exercise on metabolism.
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