Postprandial hypertriglyceridemia activates microglia to promote satiety via an ASC dependent signaling.

Abstract

Reactive microglia are commonly considered neurotoxic and detrimental for brain functioning. Chronic consumption of a high-fat diet strongly activates microglia, disrupts the central control of energy metabolism, contributes to obesity, and promotes cognitive decline. In this study we report an unexpected beneficial function of microglia reaction at the time scale of a meal, whereby they promote satiety in a macronutrient-dependent manner. We show that murine microglia react to ingested dietary fat within three hours. Specifically, postprandial hypertriglyceridemia induced microglial hyper-ramification alongside with a transcriptional reprogramming promoting communication with neurons. This effect occurs in discrete brain areas, including the hypothalamus and the brainstem, which control hunger. Remarkably, microglia-specific genetic ablation of Apoptosis-associated Speck-like protein containing a CARD (named ASC), a master regulator of metabolism, immune function and cell shape, profoundly alters satiety following high-fat food consumption. These results reveal that microglia engage an immune signaling pathway to rapidly alert the neural circuits and activate an anorectic response that limits overconsumption of dietary fat. Unexpectedly, this regulatory process is sexually dimorphic, present in males only. Furthermore, we found that the postprandial microglial reaction is bypassed during obesity, providing a new therapeutic target to treat maladaptive eating disorders.

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BibTeX RIS

BibTeX

@misc{salvi2026postprandial,
  title = {{Postprandial hypertriglyceridemia activates microglia to promote satiety via an ASC dependent signaling.}},
  author = {J. Salvi and E. Nedelec and L. Leret and F. Lienard and T. Landre and S. Ben Fradj and V. Garcia and V. Gigot and B. Patris and V. Pires and A. Polizzi and C. Sanchez and T. Gautier and H. Guillou and T. Heurtaux and V. Petrilli and C. Blouet and M. T. Heneka and F. Rassendren and C. Rovere and E. Audinat and H. E. Hirbec and V. Compan and D. Trompier and A. Benani},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.04.756524},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.04.756524v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Postprandial hypertriglyceridemia activates microglia to promote satiety via an ASC dependent signaling.
AU  - J. Salvi
AU  - E. Nedelec
AU  - L. Leret
AU  - F. Lienard
AU  - T. Landre
AU  - S. Ben Fradj
AU  - V. Garcia
AU  - V. Gigot
AU  - B. Patris
AU  - V. Pires
AU  - A. Polizzi
AU  - C. Sanchez
AU  - T. Gautier
AU  - H. Guillou
AU  - T. Heurtaux
AU  - V. Petrilli
AU  - C. Blouet
AU  - M. T. Heneka
AU  - F. Rassendren
AU  - C. Rovere
AU  - E. Audinat
AU  - H. E. Hirbec
AU  - V. Compan
AU  - D. Trompier
AU  - A. Benani
PY  - 2026
DA  - 2026/10/04
PB  - bioRxiv
DO  - 10.64898/2026.10.04.756524
UR  - https://www.biorxiv.org/content/10.64898/2026.10.04.756524v1
AB  - Reactive microglia are commonly considered neurotoxic and detrimental for brain functioning. Chronic consumption of a high-fat diet strongly activates microglia, disrupts the central control of energy metabolism, contributes to obesity, and promotes cognitive decline. In this study we report an unexpected beneficial function of microglia reaction at the time scale of a meal, whereby they promote satiety in a macronutrient-dependent manner. We show that murine microglia react to ingested dietary fat within three hours. Specifically, postprandial hypertriglyceridemia induced microglial hyper-ramification alongside with a transcriptional reprogramming promoting communication with neurons. This effect occurs in discrete brain areas, including the hypothalamus and the brainstem, which control hunger. Remarkably, microglia-specific genetic ablation of Apoptosis-associated Speck-like protein containing a CARD (named ASC), a master regulator of metabolism, immune function and cell shape, profoundly alters satiety following high-fat food consumption. These results reveal that microglia engage an immune signaling pathway to rapidly alert the neural circuits and activate an anorectic response that limits overconsumption of dietary fat. Unexpectedly, this regulatory process is sexually dimorphic, present in males only. Furthermore, we found that the postprandial microglial reaction is bypassed during obesity, providing a new therapeutic target to treat maladaptive eating disorders.
ER  -

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