Biology subjects

Garreau, A.

Publications and source records attributed to Garreau, A..

4 recordsLinked to original sources

bioRxiv2026

Extracellular DNASE1L3 dysfunction fuels obesity-driven inflammation and metabolic syndrome

Obesity, a global health crisis affecting 16% of the world population, is characterized by chronic inflammation that contributes to health complications such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Emerging evidence suggests that self-DNA released from dying cells aberrantly activates inflammatory responses during obesity. However, the role of extracellular deoxyribonucleases (DNASEs), which at steady state regulate abundance of extracellular self-DNA, remains poorly understood in this context. Here, we show that individuals with obesity exhibit elevated levels of circulating cell-free DNA (cfDNA) with a distinctive end-motif signature, anti-DNASE1L3 autoantibodies and a reduction in circulating DNASE activity. These cfDNA alterations correlate with the severity of obesity and can be corrected by therapeutic intervention such as bariatric surgery. Similarly, mice fed a high-fat diet (HFD) displayed increased cfDNA levels and decreased DNASE activity. Genetic deficiency of the extracellular nuclease DNASE1L3 in mice worsened HFD-induced metabolic complications, including glucose intolerance, insulin resistance, MASLD, and metabolic tissue inflammation. Conversely, targeted supplementation of DNASE1L3 in the liver using adeno-associated viral vectors protected obese mice from developing MASLD and liver inflammation. These findings uncover a novel role of DNASE1L3 in controlling obesity-associated inflammation and its potential therapeutic use for preventing metabolic disease.

pathology↗

bioRxiv2025

Transcriptome remodeling and adaptive preservation of muscle protein content in hibernating black bears

Hibernation is an energy-saving adaptation associated with physical inactivity. In contrast to most mammals, hibernating bears demonstrate limited loss of muscle mass and protein content over the prolonged periods of immobility and fasting during winter. This suggests that bears have natural adaptive mechanisms preserving muscle mass and functionality. To identify transcriptional changes that underlie molecular mechanisms attenuating muscle loss, we conducted a large-scale gene expression profiling (14,199 genes) by transcriptome sequencing in quadriceps of adult black bears, comparing hibernating animals (n=5) and summer active animals (n=5). Gene set enrichment analysis showed significant positive correlation between hibernating phenotype and expression changes of genes involved in translation, ribosome and the mTORC1 mediated signaling. In contrast, coordinated transcriptional reduction was detected for genes involved in catabolism of branched chain amino acid (BCAA) suggesting preservation of BCAA. These findings imply maintenance of protein biosynthesis through the mTORC1 signaling positively activated by availability of BCAA in muscle during hibernation. Support for this conclusion comes from overexpression of RRAGD and RRAGB, crucial regulator of the mTORC1 response to leucine availability, and up regulation of EIF4B, downstream target of the mTORC1 signaling. Consistent with the mTORC1 suppression of autophagy-dependent protein degradation, MAP1LC3A and ULK1 were down regulated in hibernating muscle. The maintenance of protein biosynthesis and decrease in protein catabolism through the mTORC1 signaling as response to BCAA availability likely contribute to the preservation of muscle protein through prolonged periods of immobility and fasting during hibernation.

genomics↗

bioRxiv2023

Thermal environment and ecological interactions modulate the importance of evolution in response to warming

Understanding the interaction between evolutionary history, the current abiotic environment, and biotic interactions is critical for a more nuanced understanding of the response of communities to anthropogenic stressors. We leveraged a long term experiment manipulating temperature in mesocosms containing communities of phytoplankton and zooplankton to examine how evolution in response to long-term community warming affects consumer-resource dynamics at different temperatures. We showed that the evolution in response to warming depends on both the current thermal environment, as well as the presence of interactions between consumers and resources. We also demonstrated that evolution influences the outcomes of current ecological dynamics. For each consumer-resource pair, the effects of evolution were temperature-dependent, but both the effects and the temperature dependence itself additionally depended upon the identity of evolving species in each pair. Evolution resulted on a win-win situation for the first resource species: across all temperatures, this resource was more fit and the consumer was less successful, with fitness gains peaking at intermediate temperatures. For this resource species our results supported the "hotter is better" hypothesis, especially at moderate or intermediate temperatures, while "hotter is worse" for the consumer. In the second species pair, patterns were more complex. Warm-origin populations of both the second resource and the consumer generally failed to show improved fitness. Overall, our results show that evolution altered resource and consumer fitness, but these effects were dependent on the current combination of abiotic and biotic conditions.

ecology↗

bioRxiv2020

Intraspecific diversity loss in a predator species alters prey community structure and ecosystem functions

AO_SCPLOWBSTRACTC_SCPLOWLoss in intraspecific diversity can alter ecosystem functions, but the underlying mechanisms are still elusive, and intraspecific biodiversity-ecosystem function relationships (iBEF) have been restrained to primary producers. Here, we manipulated genetic and functional richness of a fish consumer (Phoxinus phoxinus), to test whether iBEF relationships exist in consumer species, and whether they are more likely sustained by genetic or functional richness. We found that both genotypic and functional richness affected ecosystem functioning, either independently or in interaction. Loss in genotypic richness reduced benthic invertebrate diversity consistently across functional richness treatments, whereas it reduced zooplankton diversity only when functional richness was high. Finally, both losses in genotypic and functional richness altered essential functions (e.g. decomposition) through trophic cascades. We concluded that iBEF relationships lead to substantial top-down effects on entire food chains. The loss of genotypic richness impacted ecological properties as much as the loss of functional richness, probably because it sustains "cryptic" functional diversity.

ecology↗