Biology subjects

Acar, N.

Publications and source records attributed to Acar, N..

3 recordsLinked to original sources

bioRxiv2025

Regulation of lipid metabolism is a primordial function of STING

The stimulator of interferon genes (STING) is a pivotal regulator of type I interferon (IFN) responses. Although the IFN system is confined to vertebrates, STING is present across metazoans and in some unicellular eukaryotes, suggesting involvement in distinct functions prior to vertebrate divergence. We here explored the conservation of STING-mediated regulation of polyunsaturated fatty acid (PUFA) metabolism. We found that tested STING homologs from vertebrates, invertebrates, and unicellular eukaryotes interacted with the fatty acid desaturase 2 (FADS2) rate-limiting enzyme in PUFA metabolism and subsequent functional outputs. The ability to regulate lipid metabolism did not correlate with antiviral activity, suggesting that the cooptation of this metabolic pathway by the IFN-based immune system is independent of STING-associated immune responses. Thus, STING-mediated metabolic regulation is an evolutionarily conserved feature and a primordial STING function.

immunology↗

bioRxiv2025

Maternal n-3 PUFA deficiency alters brain fatty acid and oxylipin profiles across perinatal development in offspring

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), are essential for optimal neurodevelopment through their effect on neuronal proliferation, neurite outgrowth and synaptogenesis. Emerging evidence highlights that brain PUFAs are metabolized in oxylipins, the bioactive oxidized PUFA metabolites known to regulate inflammatory processes. Recent data highlighted that both PUFA and oxylipin profiles are modulated in the adult male brain by dietary PUFA content. However, little is known on the impact of maternal dietary n-3 PUFA intake during the perinatal period and the neurodevelopmental profile of brain fatty acids and associated oxylipins in offspring, and whether these effects differ between sexes. To address this question, we first measured fatty acid levels in the placenta and embryonic brain of male and female offspring of mothers fed a sufficient or deficient diet in n-3 PUFAs at embryonic day (E)17.5. Then, fatty acids and oxylipins were measured at different post-natal stages, in the brain at P0 and P7, and in the hippocampus at P14 and P21, in both male and female offspring. Our results show that maternal n-3 PUFA dietary deficiency alters fatty acid profiles as early as E17.5 in both the placenta and the brain. Furthermore, dietary intervention affects both fatty acid and oxylipin profiles throughout postnatal brain development, with notable sex-specific differences. These findings underscore the critical importance of adequate maternal n-3 PUFA intake during the perinatal period for maintaining an optimal PUFA and oxylipin profiles, with potential implications for fetal and postnatal brain development.

neuroscience↗

bioRxiv2024

The food grade bacterium Lactobacillus helveticus VEL12193 promotes autophagy by releasing membrane vesicles

Autophagy-related processes, including canonical macroautophagy, are crucial for maintaining cellular homeostasis in eukaryotic organisms. Alterations or reduced activity of these processes have been strongly linked to a broad range of human diseases including inflammatory bowel disease (IBD) and age-related diseases such as age-related macular degeneration - a disease that affect the central area of the retina. In contrast, long-term autophagy stimulation appears to be safe and to extend lifespan in model organisms such as mice. Thus, enhancing autophagy represents a promising strategy for promoting healthy aging. Several studies indicate that the gut microbiota can influence host autophagy at the gut mucosa but also in peripheral organs, and some microbial metabolites have been identified as autophagy modulators. In this study, we studied the capacity of bacterial species commonly used in food fermentation (ferments) or health (probiotics) to modulate host autophagy by in vitro and in vivo approaches. In vitro screening of a library of 11 bacterial strains revealed a strain-dependent ability of lactobacilli and bifidobacteria to stimulate autophagy in human epithelial cells. The Lactobacillus helveticus strain VEL12193, isolated from cheese, emerged as the most effective inducer of autophagy. In vivo experiment using mice showed that long-term dietary supplementation with L. helveticus VEL12193 was associated with stimulation of autophagy in the gut mucosa and retina. We identified L. helveticus-derived membrane vesicles (MVs) as a bacterial component involved in bacterial-induced autophagy in epithelial and immune cells. Moreover, in vitro, we demonstrated that L. helveticus VEL12193 possesses immunomodulatory properties in macrophages, as well as in the gut mucosa of a preclinical mouse model of IBD. With this study we provide robust proof of concept that ferments/probiotics can stimulate autophagy at the organism scale and that this phenotype involved MVs. In addition, we identify L. helveticus VEL12193 as a candidate strain of interest for the design of healthy-aging strategies.

microbiology↗