Recent Advances in Studying Age-Associated Lipids Alterations and Dietary Interventions in Mammals

Lipids are involved in a broad spectrum of canonical biological functions, from energy supply and storage by triacylglycerols to membrane formation by sphingolipids, phospholipids and glycolipids. Because of this wide range of functions, there is an overlap between age-associated processes and lipid pathways. Lipidome analysis revealed age-related changes in the lipid composition of various tissues in mice and humans, which were also influenced by diet and gender. Some changes in the lipid profile can be linked to the onset of age-related neurodegenerative diseases like Alzheimer’s disease. Furthermore, the excessive accumulation of lipid storage organelles, lipid droplets, has significant implications for the development of inflammaging and non-communicable age-related diseases. Dietary interventions such as caloric restriction, time-restrictive eating, and lipid supplementation have been shown to improve pertinent health metrics or even extend life span and thus modulate aging processes.

Link between serum lipid signature and prognostic factors in COVID-19 patients

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including—among others—four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.

M6A methylation of DEGS2, a key ceramide-synthesizing enzyme, is involved in colorectal cancer progression through ceramide synthesis

N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulator in cancer. However, the understanding of m6A modification on lipid metabolism regulation in colorectal cancer (CRC) is very limited. Here, we observed that human CRCs exhibited increased m6A mRNA methylation mediated by dysregulation of m6A erasers and readers. By performing methylated RNA-immunoprecipitation sequencing (MeRIP-seq) and transcriptomic sequencing (RNA-seq), we identified DEGS2 as a downstream target of m6A dysregulation. Overexpression or knockdown of DEGS2 confirmed the role of DEGS2 in proliferation, invasion and metastasis of CRC both in vitro and in vivo. Mechanistic studies identified the specific m6A modification site within DEGS2 mRNA, and mutation of this target site was found to drastically enhance the proliferative and invasive ability of CRC cells in vitro and promote tumorigenicity in vivo. Lipidome analysis showed that lipid metabolism was dysregulated in CRC. Moreover, ceramide synthesis was suppressed due to DEGS2 upregulation mediated by m6A modification in CRC tissues. Our findings highlight that the function of DEGS2 m6A methylation in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology.

Biomarkers predictive of long-term fertility found in vaginal lipidome of gilts at weaning

A marker indicative of fertility potential of replacement gilts early in development would decrease culling rates in the sow herd, improve sow herd reproductive efficiency, and reduce production costs. The objective of this study was to determine if vaginal lipid profiles at 21 d postnatal (PN) could predict sow reproductive performance. Vaginal swabs of the anterior vagina were taken at 21 ± 4 d PN from gilts born on a commercial sow production facility for lipidomic analysis. Animals were followed prospectively for two years and assigned to reproductive performance categories based on observation of estrus or piglets weaned per sow per year (PSY) across two farrowings. Lipids were extracted from cellular material collected with swabs taken from high fertility (HF; n=28; ≥26 PSY) and infertile (IF; n=34; no estrus, no pregnancy) animals and multiple reaction monitoring (MRM)-profiling was used for lipidome analysis. Relative abundance of arachidonic acid (ARA, C20:4) and docosahexaenoic acid (DHA, C22:6) were lower (P<0.05) in IF gilts than HF gilts, whereas abundance of the free fatty acids cerotic (C26:0), ximenic (C26:1), and nonadecanoic (C19:0) acids were greater (P<0.05) in IF gilts. Additionally, eicosapentaenoic acid (C20:5) a precursor of prostaglandins was higher (P<0.05) in IF gilts. The perspective of having a panel of lipids captured with vaginal swabs at weaning that can predict reproductive efficiency of gilts shows promise and warrants future research in this area.

Biogenesis of Outer Membrane Vesicles Concentrates the Unsaturated Fatty Acid of Phosphatidylinositol in Capnocytophaga ochracea

Bacterial outer membrane vesicles (OMVs) are spherical lipid bilayer nanostructures released by bacteria that facilitate oral biofilm formation via cellular aggregation and intercellular communication. Recent studies have revealed that Capnocytophaga ochracea is one of the dominant members of oral biofilms; however, their potential for OMV production has yet to be investigated. This study demonstrated the biogenesis of OMVs in C. ochracea associated with the concentration of unsaturated fatty acids of phosphatidylinositol (PI) and characterized the size and protein profile of OMVs produced at growth phases. Transmission electron microscopy showed isolated spherical structures from cells stained with heavy metals, indicating the production of OMVs with a size ranging from 25 to 100 nm. Lipidome analysis revealed the presence of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, and PI as the main lipids. Some unsaturated fatty acids of PI were present specifically in OMV and little in the outer membrane, suggesting that OMVs are generated from a specific region of the membrane through blebbing rather than a random process such as cell lysis. Furthermore, the lack of similar PI accumulation in the OMV of Porphyromonas gingivalis suggests that C. ochracea has a different biogenesis mechanism. The blebbing mechanism was further supported by higher OMV production occurring at the exponential phase in comparison to the stationary phase, where cell lysis is more likely to occur. Further, comparative protein profile of OMVs isolated under different growth phases may indicate that the OMV cargo does not largely vary with growth phases. The present study provides a basis for further understanding the roles of C. ochracea OMVs in oral biofilms as well as systemic diseases that C. ochracea involves.

Biomarkers predictive of long-term fertility found in vaginal lipidome of gilts at weaning

Background A marker indicative of fertility potential of replacement gilts early in development would decrease culling rates in the sow herd, improve sow herd reproductive efficiency, and reduce production costs. The objective of this study was to determine if vaginal lipid profiles at 21 d postnatal (PN) could predict sow reproductive performance. Methods Vaginal swabs of the anterior vagina were taken at 21 ± 4 d PN from gilts born on a commercial sow production facility for lipidomic analysis. Animals were followed prospectively for two years and assigned to reproductive performance categories based on observation of estrus or piglets weaned per sow per year (PSY) across two farrowings. Results Lipids were extracted from cellular material collected with swabs taken from high fertility (HF; n = 28; ≥26 PSY) and infertile (IF; n = 34; no estrus, no pregnancy) animals and multiple reaction monitoring (MRM) profiling was used for lipidome analysis. Relative abundance of arachidonic acid (ARA, C20:4) and docosahexaenoic acid (DHA, C22:6) were lower (P < 0.05) in IF gilts than HF gilts, whereas abundance of the free fatty acids cerotic (C26:0), ximenic (C26:1), and nonadecanoic (C19:0) acids were greater (P < 0.05) in IF gilts. Additionally, eicosapentaenoic acid (C20:5) a precursor of prostaglandins was also higher (P < 0.05) in IF gilts. Conclusions The perspective of having a panel of lipids captured with vaginal swabs at weaning that can predict reproductive efficiency of gilts shows promise and warrants future research in this area.