A Female-Specific Microglial Redox Program Gates Susceptibility to Obesity
- 1University of Bordeaux
Abstract
Chronic consumption of energy-dense, high-fat foods persistently exposes hypothalamic circuits that govern body weight to nutrient excess, progressively altering their activity and thereby promoting obesity. Microglia, the brain resident immune cells, sense circulating lipids, but how their intracellular metabolic programs adapt to chronic dietary excess, and how this contributes to obesity risk, is unclear. Here, we reveal a sex-dependent control of calorie overload by hypothalamic microglial cells. In females, but not males, microglia engage a protective metabolic program with increased antioxidant capacity and mitochondrial network remodeling, conferring resistance to early weight gain. Over time, activation of mTORC1 signaling in microglia disrupts mitochondrial functions and dismantles this transient resilience, culminating in weight gain. These findings identify microglial mTORC1 as a sex-specific switch between resilience and vulnerability to obesity and position microglial metabolism as a tractable target for sex-informed weight control.
Related
- A Microglial Regulatory Program Linked to Neuropsychiatric Disorders
- A self-limiting, TREM2-dependent anabolic program confers microglial resilience in Alzheimer's disease
- Female-Biased IL-17/STAT3 Signaling Marks Dementia-Associated Microglial Inflammation in Alzheimer's Disease
- Genetic and expression evidence supports FTO rs9939609 as a key susceptibility marker for type 2 diabetes and obesity in Thai adults
- Glucocorticoid dynamics predict susceptibility and resilience to traumatic stress in male and female rats.
BibTeX
@misc{kyriakidou2026femalespecific,
title = {{A Female-Specific Microglial Redox Program Gates Susceptibility to Obesity}},
author = {E. Kyriakidou and G. Cutugno and G. Duranthon and P. Gaikwad and E. Archontoulaki and J. Vergne and C. Torrent and E. Garbaye and S. Lillo and O. Kassem and D. Jimenez-Blasco and P. Zizzari and V. Simon and S. James and A. Coutansais and N. Dupuy and T. Leste-Lasserre and G. Laplagne and M. David and J. Ezan and F. Martins and A. Brochard and G. Adisurja and B. Salin and J. A. Reisz and G. Marsicano and C. Quarta and L. Groc and V. U. Nagerl and J. P. Bolanos and R. Rua and A. D'Alessandro and A. Mourier and C. Allard and D. Cota and A. Nadjar},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749380},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749380v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Female-Specific Microglial Redox Program Gates Susceptibility to Obesity
AU - E. Kyriakidou
AU - G. Cutugno
AU - G. Duranthon
AU - P. Gaikwad
AU - E. Archontoulaki
AU - J. Vergne
AU - C. Torrent
AU - E. Garbaye
AU - S. Lillo
AU - O. Kassem
AU - D. Jimenez-Blasco
AU - P. Zizzari
AU - V. Simon
AU - S. James
AU - A. Coutansais
AU - N. Dupuy
AU - T. Leste-Lasserre
AU - G. Laplagne
AU - M. David
AU - J. Ezan
AU - F. Martins
AU - A. Brochard
AU - G. Adisurja
AU - B. Salin
AU - J. A. Reisz
AU - G. Marsicano
AU - C. Quarta
AU - L. Groc
AU - V. U. Nagerl
AU - J. P. Bolanos
AU - R. Rua
AU - A. D'Alessandro
AU - A. Mourier
AU - C. Allard
AU - D. Cota
AU - A. Nadjar
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749380
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749380v1
AB - Chronic consumption of energy-dense, high-fat foods persistently exposes hypothalamic circuits that govern body weight to nutrient excess, progressively altering their activity and thereby promoting obesity. Microglia, the brain resident immune cells, sense circulating lipids, but how their intracellular metabolic programs adapt to chronic dietary excess, and how this contributes to obesity risk, is unclear. Here, we reveal a sex-dependent control of calorie overload by hypothalamic microglial cells. In females, but not males, microglia engage a protective metabolic program with increased antioxidant capacity and mitochondrial network remodeling, conferring resistance to early weight gain. Over time, activation of mTORC1 signaling in microglia disrupts mitochondrial functions and dismantles this transient resilience, culminating in weight gain. These findings identify microglial mTORC1 as a sex-specific switch between resilience and vulnerability to obesity and position microglial metabolism as a tractable target for sex-informed weight control.
ER -