Biology subjects

Everard, A.

Publications and source records attributed to Everard, A..

3 recordsLinked to original sources

bioRxiv2025

Fecal Dysosmobacter spp. concentration is linked to plasma lipidome in insulin-resistant individuals with overweight, obesity and metabolic syndrome

BackgroundObesity is reaching epidemic proportions worldwide. This excessive increase of adipose tissue is a risk factor for the development of multiple diseases and premature death. Amongst associated diseases, metabolic syndrome is one of the main comorbidities of obesity. In this context, the gut microbiota has been recognized as both shaping and responding to host energy metabolism. Recently metabolomics has emerged as a powerful tool to capture a snapshot of the metabolites present in a specific tissue, offering new insights into host-microbiota interactions. Integrating metabolomics with gut microbiota studies could help us better understand how specific species impact on host metabolomic profile. Dysosmobacter welbionis has been identified as a promising next generation beneficial bacteria with potential effects on fat mass and glucose metabolism in mice, and fecal Dysosmobacter spp concentration was inversely correlated to body mass index fasting glucose and plasmatic HbA1c in humans. MethodsConcentration of Dysosmobacter spp was quantified by qPCR in the stools of insulin resistant overweight/obese participants with a metabolic syndrome and plasma metabolites were analyzed using untargeted metabolomics. Correlations between Dysosmobacter spp fecal abundance and the 1169 identified plasma metabolites were uncovered using Spearman correlations followed by a false discovery rate correction. ResultsInterestingly, among the detected metabolites, Dysosmobacter spp was exclusively associated with lipid molecules, primarily structural lipids involved in membrane formation. This finding aligns with previous in vivo studies highlighting lipid profile alterations in multiple tissues of mice treated with this bacterium. ConclusionThese results suggest that Dysosmobacter spp plays a specific role in host lipid metabolism. Further studies are needed to elucidate the underlying mechanisms and assess its potential therapeutic applications.

physiology↗

bioRxiv2023

NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis

The N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) catalyzes the production of N-acylethanolamines (NAEs), a family of endogenous bioactive lipids, which are involved in various biological processes ranging from neuronal functions to energy homeostasis and feeding behaviors. Reward-dependent behaviors depend on the dopamine (DA) transmission between the ventral tegmental area (VTA) and the nucleus accumbens (NAc) which conveys reward-values and scales reinforced behaviors. However, whether and how NAPE-PLD may contribute to the regulation of feeding and reward-dependent behaviors has not been investigated yet. This biological question is of paramount importance since NAEs are altered in obesity and metabolic disorders. Here, we show that transcriptomic meta-analysis highlights a potential role for NAPE-PLD within the VTA[->]NAc circuit. Using brain-specific invalidation approaches, we report that the integrity of NAPE-PLD is required for the proper homeostasis of NAEs within the midbrain VTA and it affects food-reward behaviors. Moreover, region-specific knock-down of NAPE-PLD in the VTA resulted in enhanced food-reward seeking and reinforced behaviors which were associated with increased in vivo DA release dynamics in response to both food and non-food-related rewards together with heightened tropism towards food consumption. Furthermore, midbrain knock-down of NAPE-PLD, which led to increased energy expenditure and adapted nutrients partitioning, elicited a relative protection against high-fat diet-mediated body fat gain and obesity-associated metabolic features. In conclusion, these findings unravel a new key role of VTA NAPE-PLD in shaping DA-dependent events, feeding behaviors and energy homeostasis, thus providing new insights on the regulation of body metabolism. Highlights- NAPE-PLD and NAEs are enriched in the VTA and regulate food-reinforced behaviors and reward processes. - NAPE-PLD scales in vivo VTA[->]NAc dopamine dynamics. - NAPE-PLD in the VTA contributes to whole-body energy balance and metabolic efficiency. - Downregulation of VTA NAPE-PLD ameliorates obesity-associated metabolic features.

neuroscience↗

bioRxiv2018

Microbiome inhibition of IRAK-4 by trimethylamine mediates metabolic and immune benefits in high-fat-diet-induced insulin resistance

The global type 2 diabetes epidemic is a major health crisis and there is a critical need for innovative strategies to fight it. Although the microbiome plays important roles in the onset of insulin resistance (IR) and low-grade inflammation, the microbial compounds regulating these phenomena remain to be discovered. Here, we reveal that the microbiome inhibits a central kinase, eliciting immune and metabolic benefits. Through a series of in vivo experiments based on choline supplementation, blocking trimethylamine (TMA) production then administering TMA, we demonstrate that TMA decouples inflammation and IR from obesity in the context of high-fat diet (HFD) feeding. Through in vitro kinome screens, we reveal TMA specifically inhibits Interleukin-1 Receptor-associated Kinase 4 (IRAK4), a central kinase integrating signals from various toll-like receptors and cytokine receptors. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells, and improves mouse survival after a lipopolysaccharide-induced septic shock. Consistent with this, genetic deletion and chemical inhibition of IRAK4 result in similar metabolic and immune improvements in HFD. In summary, TMA appears to be a key microbial compound inhibiting IRAK4 and mediating metabolic and immune effects with benefits upon HFD. Thereby we highlight the critical contribution of the microbial signalling metabolome in homeostatic regulation of host disease and the emerging role of the kinome in microbial-mammalian chemical crosstalk.

systems biology↗