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

Han Jiao; Jarne Jermei; Xian Liang; Hendrik J.P. van der Zande; Frank Vrieling; Valentina Sophia Rumanova; Milan Dorscheidt; Felipe Corrêa‐da‐Silva; Anhui Wang; Ewout Foppen; Alberto M. Pereira; Dirk Jan Stenvers; TieMin LIU; Kimberly Bonger; Rinke Stienstra; Zhi Zhang; Andries Kalsbeek; Chun‐Xia Yi

doi:10.1016/j.celrep.2025.116380

ImmunologyCell ReportsOct 1, 2025

Peer-reviewed journal article

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

Han Jiao iD, Jarne Jermei iD, Xian Liang iD, Hendrik J.P. van der Zande iD, Frank Vrieling iD, Valentina Sophia Rumanova iD, Milan Dorscheidt, Felipe Corrêa‐da‐Silva iD, Anhui Wang, Ewout Foppen iD, Alberto M. Pereira iD, Dirk Jan Stenvers iD, TieMin LIU, Kimberly Bonger, Rinke Stienstra iD, Zhi Zhang iD, Andries Kalsbeek iD, Chun‐Xia Yi iD

Abstract

Time-restricted eating has shown promise for improving metabolic health in obese humans via incompletely resolved mechanisms. In this study, we investigated how time-restricted feeding (TRF) at different times of the day affects microglial immunometabolism using Wistar rats. We found that in high-fat diet (HFD)-fed obese rats, TRF during the active phase reduced fat mass, altered rhythmicity of the microglial transcriptome, and prevented an increase in hypothalamic microglia. These effects were dampened or absent with TRF during the resting phase. However, a HFD-induced microglial immunometabolic phenotype, characterized by reduced electron transport chain and increased lipid metabolism gene expression, and metabolic inflexibility, was not reversed by TRF in either the active or resting phase, indicating that reprogrammed microglial metabolism in obesity is a persistent cellular functional change that requires further study.

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