Limited microglial metabolic improvement with time-restricted feeding in diet-induced obesity

Han Jiao, Jarne Jermei, Xian Liang, Felipe Correa-da-Silva, Milan Dorscheidt, Valentina Sophia Rumanova, Delaram Poormoghadam, Ewout Foppen, Nikita Korpel, Dirk Jan Stenvers, Alberto Pereira Arias, Tiemin Liu, Zhang Zhi, Andries Kalsbeek, Chun-Xia Yi
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Abstract

Time-restricted eating has shown promise for improving metabolic health in obese humans. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects the microglial brain immune function using Wistar rats. We found that in high-fat diet (HFD)-induced obesity, TRF during the active phase of rats is effective in reducing fat mass, enhancing the rhythmicity of the microglial transcriptome, and preventing an increase in microglial cell number. These effects are not seen with TRF during the resting phase. However, the HFD-induced activation of microglial metabolic pathways was not reversed by TRF in either the active or resting phase, indicating that the reprogrammed microglial metabolism in obesity is a persistent cellular functional change that might form a metabolic memory and play a role in body weight regain upon discontinuation of restricted eating.
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限时进食对饮食诱发肥胖症的小胶质细胞代谢改善有限
限时进食有望改善肥胖人群的代谢健康。在这项研究中,我们利用 Wistar 大鼠研究了一天中不同时间段的限时进食(TRF)如何影响小胶质细胞的脑免疫功能。我们发现,在高脂饮食(HFD)诱导的肥胖症中,大鼠活动期的 TRF 能有效减少脂肪量,增强小胶质细胞转录组的节律性,并防止小胶质细胞数量的增加。在静止期使用 TRF 则不会产生这些效果。然而,无论是在活动期还是静息期,TRF 都不能逆转 HFD 诱导的小胶质细胞代谢途径的激活,这表明肥胖症中重新编程的小胶质细胞代谢是一种持续的细胞功能变化,可能会形成代谢记忆,并在停止限制进食后导致体重反弹。
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