Biology subjects

Di Marzo, V.

Publications and source records attributed to Di Marzo, V..

4 recordsLinked to original sources

bioRxiv2025

Circadian Disruption Elicits Sex-Specific Gut Microbiota, Endocannabinoidome and Lipid Mediator Responses

Circadian disruption is a pervasive environmental stressor that increases susceptibility to metabolic and inflammatory diseases, yet sex-specific adaptive strategies remain poorly understood. Here, we show that constant light (LL) exposure alters gut microbial communities and triggers sex- and tissue-specific host adaptations in the endocannabinoidome and other bioactive lipids. Using 16S rRNA sequencing, short chain fatty acid (SCFA) quantification, LC-MS/MS lipidomics, and cytokine profiling, we identified divergent coping strategies across brain, metabolic and intestinal tissues and reproductive organs. In females, LL induced microbial restructuring, with enrichment of Rikenellaceae, Butyricicoccaceae, and Alistipes, but these changes were uncoupled from short-chain fatty acids (SCFA) output. Also, they engaged N-acylethanolamine (NAE)-driven endocannabinoidome signaling in the brain (AEA, DHEA, OEA, PEA, SEA), accompanied by omega-6 prostaglandin upregulation and increased cytokines (IL-5, IFN-{gamma}, MIP-2). The 2-monoacyl glycerols (2-MAGs) increased selectively in liver and skeletal muscle, reflecting tissue-specific lipid remodeling. In males, microbial shifts were limited (e.g., Ruminococcaceae depletion, Tuzzerella enrichment), yet LL triggered robust metabolic adaptation resulting in elevated SCFA levels (isobutyric, butyric, isovaleric, valeric acids) in faeces and elevation of several DHA-derived bioactive lipids in different intestinal tissues Few alterations in brain bioactive lipids were found, while several 2-MAGs were elevated skeletal muscles and testes. In contrast, several oxylipins were decreased within subcutaneous but not other adipose tissue depots. Together, the data shows that changes in bioactive lipid levels in response to circadian rhythm disruption are organ- and sex-specific as are alterations in microbiota populations, positioning sex as a key determinant of responses to circadian stress.

biochemistry↗

bioRxiv2025

Fetal Bovine and Calf Serums Differ in Their Contents of Endocannabinoids, Unsaturated Fatty Acids, Monoacyl-Glycerols, N-Acyl-Ethanolamines, Oxylipins and Cytokines.

Cell culture relies heavily on serum supplementation, but serum composition makes it difficult to ensure reproducibility and consistency of experimental results. Consequently, research groups must test multiple batches to ensure the functionality and reproducibility of their models of their models. The commonly used serums are fetal bovine serums (FBS) and calf serums (CS), which have been recognized as crucial in modulating cellular processes. While having been utilized for decades, little information is known about their respective lipid mediator contents. This study explored the presence of several major bioactive lipids involved in the regulation of inflammation, metabolism, differentiation, immune response, neuroprotection, and vascular homeostasis. These included polyunsaturated fatty acids, monoacylglycerols (MAGs), N-acyl-ethanolamines (NAEs), and oxylipins. As compared to FBS, CS samples were enriched in most fatty acids except for arachidonic acid. The levels of the endocannabinoids 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA) followed the same pattern as arachidonic acid. On the other hand, most lipoxygenase-derived mediators, including, leukotriene B4, showed higher abundance in CS. Accordingly, CS serum activated the random migration of human neutrophils to a much greater extent than FBS, an effect attenuated by the BLT1 receptor antagonist CP 105,696. These findings highlight how bovine serum lipid composition is a major determinant modulating cellular responses and might thus impact experimental reproducibility. The data presented herein will help key insights beyond conventional cell culture optimization and might represent key features to consider when planning in cellulo experiments across numerous fields, also beyond immunology.

cell biology↗

bioRxiv2023

Astrocytes modulate neuronal development by S100A6 signaling

Neuronal morphogenesis relies on intercellular signaling. Astrocytes release metabolites, trophic, and guidance factors to promote neuronal maturation. In contrast, the mechanisms by which astrocytes could limit and stabilize neuronal connectivity remain less explored. Here, we show cortical astrocytes to express and release S100A6, a Ca2+-binding protein ( calcyclin). Simultaneously, the majority of cortical neurons express calcyclin-binding protein (CaCyBp), a bona fide binding partner for S100A6. In neurons, CaCyBp maintains the unfolded protein response pathway, thereby controlling proteostasis. When released, S100A6 inhibits CaCyBp-mediated signaling, thus slowing protein turnover, and, consequently, neuritogenesis. S100A6-CaCyBp signaling during gestation and lactation is sensitive to the mothers nutritional status, particularly eicosapentaenoic acid intake. Thus, a member of the S100 protein family acts as an astroglia-derived morphogen, whose action on neurons is modulated by environmental factors.

neuroscience↗

bioRxiv2020

Gene Deletion Studies Reveal A Critical Role For Prostamide/Prostaglandin F2α Synthase In Prostamide F2α Formation

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide and prostaglandin F2. The importance of this enzyme, relative to the aldoketoreductase (AKR) series, in providing functional tissue prostamide F2 levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (fam213b) was accomplished by a two exon disruption. Prostamide F2 levels in WT and PM/PGFS KO mice were determined by LC/MS/MS. Intraocular pressure was measured by tonometry and outflow facility was measured by the iPerfusion method in enucleated mouse eyes. Deletion of fam213b had no observed effect on behavior, appetite, or fertility. Intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. No effect on pressure dependent outflow facility occurred, which is consistent with the typically reported prostanoid effect of increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids that raise intraocular pressure, namely prostaglandin D2 (PGD2), thromboxane A2 (TxA2). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF2 and prostamide F2 to constrain the influence of those prostanoids that raise intraocular pressure.

pharmacology and toxicology↗