Geriatric unit, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan.
Open Biol. 2020 Sep;10(9):200176. doi: 10.1098/rsob.200176. Epub 2020 Sep 16.
Since ancient days, human fasting has been performed for religious or political reasons. More recently, fasting has been employed as an effective therapy for weight reduction by obese people, and numerous studies have investigated the physiology of fasting by obese subjects. Well-established fasting markers (butyrates, BCAAs and carnitines) were considered essential energy substitutes after glycogen storage depletion. However, a recently developed metabolomic approach has unravelled previously unappreciated aspects of fasting. Surprisingly, one-third (44) of 120 metabolites investigated increase during 58 h of fasting, including antioxidative metabolites (carnosine, ophthalmic acid, ergothioneine and urates) and metabolites of entire pathways, such as the pentose phosphate pathway. Signalling metabolites (3-hydroxybutyrate and 2-oxoglutarate) and purines/pyrimidines may also serve as transcriptional modulators. Thus, prolonged fasting activates both global catabolism and anabolism, reprogramming metabolic homeostasis.
自古以来，人类禁食就一直出于宗教或政治原因。最近，禁食已被肥胖人群用作减肥的有效疗法，许多研究已经调查了肥胖受试者禁食的生理学。已确立的禁食标志物（丁酸、支链氨基酸和肉碱）被认为是在糖原储存耗尽后的重要能量替代品。然而，最近开发的代谢组学方法揭示了禁食以前未被重视的方面。令人惊讶的是，在 58 小时的禁食期间，120 种代谢物中有三分之一（44 种）增加，包括抗氧化代谢物（肌肽、牛磺酸、谷氨硫胺和尿酸盐）和整个途径的代谢物，如磷酸戊糖途径。信号代谢物（3-羟基丁酸和 2-氧戊二酸）和嘌呤/嘧啶也可能作为转录调节剂。因此，长时间禁食会激活全身的分解代谢和合成代谢，重新编程代谢稳态。
