Biology subjects

Gautron, L.

Publications and source records attributed to Gautron, L..

3 recordsLinked to original sources

bioRxiv2026

Lipid mobilization establishes metabolic tolerance and prevents autonomic collapse in infection

Survival during infection depends on both pathogen clearance and the ability to tolerate infection-induced physiological changes. Metabolic adaptations are a central component of this tolerance, but the mechanisms underlying these responses remain incompletely defined. Here, we identify white adipose tissue (WAT) lipolysis as a central regulator of metabolic tolerance to infection. In patients with sepsis, higher circulating non-esterified fatty acid (NEFA) levels were associated with reduced mortality. In mouse models of polymicrobial sepsis, infection induced robust adipose lipolysis and increased circulating NEFAs. Genetic ablation of adipose triglyceride lipase (ATGL) in adipose tissue impaired lipolysis, leading to hypothermia, bradycardia, and increased mortality without altering immune cell populations or pathogen burden, consistent with a defect in tolerance rather than resistance. Mechanistically, lipolysis-derived NEFAs, but not glycerol, were required for protection, as restoring circulating NEFAs rescued autonomic stability and survival in adipose tissue ATGL-deficient mice. Infection-induced lipolysis was redundantly regulated and did not depend on any single upstream signaling pathway. Both pharmacologic activation of lipolysis using a {beta}3-adrenergic agonist and exogenous fatty acid supplementation increased circulating NEFAs, improved survival, and promoted tolerance in mice. Consistent with these findings, analysis of real-world electronic health record data demonstrated that septic patients receiving FDA-approved {beta}3-adrenergic agonists had reduced mortality or hospice discharge in a propensity-matched cohort. Together, these results identify WAT lipolysis and circulating fatty acids as key mediators of tolerance to infection and support a therapeutic strategy based on repurposing clinically available {beta}3-adrenergic agonists to improve outcomes in sepsis. One Sentence SummaryWhite adipose tissue lipolysis promotes metabolic tolerance to infection through circulating fatty acids and is associated with improved survival in sepsis

physiology↗

bioRxiv2022

FGF21 Counteracts Alcohol Intoxication by Activating Noradrenergic Neurons

Animals that consume fermenting fruit or nectar are exposed to ethanol, thus increasing their risk of injury or predation. This risk is heightened in humans, who have actively imbibed alcohol for thousands of years. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, exerts sobering or "amethystic" effects on both arousal and motor coordination without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia. FGF21 mediates it amethystic effects by directly activating the noradrenergic nervous system, which regulates arousal and alertness. These results indicate that this FGF21 liver-brain pathway evolved to protect against ethanolinduced intoxication and that it might be targeted pharmaceutically for treating acute alcohol poisoning.

neuroscience↗

bioRxiv2019

Physiology-forward identification of bile acid sensitive vomeronasal receptors

Abstract/SummaryThe mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging. These experiments revealed both broadly and narrowly tuned populations of BA-receptive VSNs with sub-micromolar sensitivities. We then developed a new physiology-forward approach for identifying AOS ligand-receptor interactions, which we call Fluorescence Live Imaging for Cell Capture and RNA-seq, or FLICCR-seq. FLICCR-seq analysis revealed 5 specific V1R-family receptors enriched in BA-sensitive VSNs. These studies introduce a powerful new approach for ligand-receptor matching and reveal biological mechanisms underlying mammalian BA chemosensation.

neuroscience↗