Postprandial hypertriglyceridemia activates microglia to promote satiety via an ASC dependent signaling
Year: 2026
Type: preprint
Abstract: Summary 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.
Authors: Juliette Salvi, Emmanuelle Nédélec, Lucie Leret, Fabienne Liénard, Tatiana Landré, Selma Ben Fradj, Valentin Garcia, Vincent Gigot, Bruno Patris, Vivien Pires, Arnaud Polizzi, Clara Sanchez, Thomas Gautier, Hervé Guillou, Tony Heurtaux, Virginie Petrilli, Clémence Blouet, Michael Heneka, François Rassendren, Carole Rovère, Etienne Audinat, Hélène Hirbec, Vincent Compan, Doriane Trompier, Alexandre Benani
Institutions: Centre National de la Recherche Scientifique, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Institut Agro Dijon, Centre des Sciences du Goût et de l'Alimentation, Inserm, Université de Montpellier, Institut de Génomique Fonctionnelle, École Nationale Vétérinaire de Toulouse, Toxicologie Alimentaire, Université de Toulouse, Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire, Centre de recherche Translationnelle en Médecine moléculaire, University of Luxembourg, Université de Lyon, Centre de Recherche en Cancérologie de Lyon, University of Cambridge, Wellcome/MRC Institute of Metabolic Science, MRC Metabolic Diseases Unit, Medical Research Council, University of Massachusetts Chan Medical School, Luxembourg Centre for Systems Biomedicine
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221718235