Abstract:SummaryAmong the phospholipase A2 (PLA2) superfamily, which typically catalyzes the sn‐2 hydrolysis of phospholipids to yield fatty acids and lysophospholipids, the secreted PLA2 (sPLA2) family contains 11 isoforms in mammals. Individual sPLA2s have unique enzymatic specificity toward fatty acids and polar heads of phospholipid substrates and display distinct tissue/cellular distributions, suggesting their distinct physiological functions. Recent studies using knockout and/or transgenic mice for a full set of … Show more
“…PLA2G1B is a secreted phospholipase A2 produced by pancreatic acinar cells, that hydrolyses phosphoglycerides to glycerophospholipids and arachidonic acid 49 . Pla2g1b knock-out mice display reduced phospholipid digestion and concurrent attenuation of diet-induced obesity, insulin resistance, and atherosclerosis, while pancreatic acinar cell-specific overexpression of Pla2g1b has been linked to increased phospholipid digestion and to exacerbation of diet-induced obesity and insulin resistance 49 . PLA2G1B is currently being investigated in clinical trials for a range of cardiometabolic conditions ( Table S1 ).…”
Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and animal product restriction (APR) for religious reasons. We find that short-term APR is associated with extensive metabolic reprogramming not detected in a control group of continuously omnivorous individuals. We identify reductions in the levels of branched-chain amino acids and of most lipid classes, driving a metabolic profile associated with decreased risk for all-cause mortality. We show that 23% of APR-associated proteins are drug targets, and highlight eight proteins displaying the greatest magnitude of change upon APR (FGF21, FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, HPGDS, SPP1). We find that APR-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention.
“…PLA2G1B is a secreted phospholipase A2 produced by pancreatic acinar cells, that hydrolyses phosphoglycerides to glycerophospholipids and arachidonic acid 49 . Pla2g1b knock-out mice display reduced phospholipid digestion and concurrent attenuation of diet-induced obesity, insulin resistance, and atherosclerosis, while pancreatic acinar cell-specific overexpression of Pla2g1b has been linked to increased phospholipid digestion and to exacerbation of diet-induced obesity and insulin resistance 49 . PLA2G1B is currently being investigated in clinical trials for a range of cardiometabolic conditions ( Table S1 ).…”
Dietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and animal product restriction (APR) for religious reasons. We find that short-term APR is associated with extensive metabolic reprogramming not detected in a control group of continuously omnivorous individuals. We identify reductions in the levels of branched-chain amino acids and of most lipid classes, driving a metabolic profile associated with decreased risk for all-cause mortality. We show that 23% of APR-associated proteins are drug targets, and highlight eight proteins displaying the greatest magnitude of change upon APR (FGF21, FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, HPGDS, SPP1). We find that APR-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention.
“…In the GI tract, it is synthesized in Paneth cells and is thought to play a role in regulating the gut microbiome (Senegas-Balas et al, 1984 ). The subsequent review delves into a more comprehensive examination of the function of sPLA2-IIA (Murakami et al, 2023 ).…”
Section: Antimicrobial Proteins—roles and Mechanisms Of Actionmentioning
The human gut houses a diverse and dynamic microbiome critical for digestion, metabolism, and immune development, exerting profound effects on human health. However, these microorganisms pose a potential threat by breaching the gut barrier, entering host tissues, and triggering infections, uncontrolled inflammation, and even sepsis. The intestinal epithelial cells form the primary defense, acting as a frontline barrier against microbial invasion. Antimicrobial proteins (AMPs), produced by these cells, serve as innate immune effectors that regulate the gut microbiome by directly killing or inhibiting microbes. Abnormal AMP production, whether insufficient or excessive, can disturb the microbiome equilibrium, contributing to various intestinal diseases. This review delves into the complex interactions between AMPs and the gut microbiota and sheds light on the role of AMPs in governing host-microbiota interactions. We discuss the function and mechanisms of action of AMPs, their regulation by the gut microbiota, microbial evasion strategies, and the consequences of AMP dysregulation in disease. Understanding these complex interactions between AMPs and the gut microbiota is crucial for developing strategies to enhance immune responses and combat infections within the gut microbiota. Ongoing research continues to uncover novel aspects of this intricate relationship, deepening our understanding of the factors shaping gut health. This knowledge has the potential to revolutionize therapeutic interventions, offering enhanced treatments for a wide range of gut-related diseases.
“…Phospholipase A2 (PLA2) and IL-6 are predictive markers for the severity of COVID-19 [172]. PLA2 cleaves the sn-2 acyl chain to yield fatty acids and lysophospholipids, leading to the production of a wide variety of mediators that modulate immunity [181] and stimulate SARS-CoV-2 infection [182]. For example, PLA2 contributes to anti-helminth defense by hydrolyzing membrane phospholipids (Th2-defence, production of IL4 and IL5 cytokines, allergy/asthma) [181].…”
Section: Immune Responses and Inflammationmentioning
The COVID-19 pandemic prompted rapid research on SARS-CoV-2 pathogenicity. Consequently, new data can be used to advance the molecular understanding of SARS-CoV-2 infection. The present bioinformatics study discusses the “spikeopathy” at the molecular level and focuses on the possible post-transcriptional regulation of the SARS-CoV-2 spike protein S1 subunit in the host cell/tissue. A theoretical protein–RNA recognition code was used to check the compatibility of the SARS-CoV-2 spike protein S1 subunit with mRNAs in the human transcriptome (1-L transcription). The principle for this method is elucidated on the defined RNA binding protein GEMIN5 (gem nuclear organelle-associated protein 5) and RNU2-1 (U2 spliceosomal RNA). Using the method described here, it was shown that 45% of the genes/proteins identified by 1-L transcription of the SARS-CoV-2 spike protein S1 subunit are directly linked to COVID-19, 39% are indirectly linked to COVID-19, and 16% cannot currently be associated with COVID-19. The identified genes/proteins are associated with stroke, diabetes, and cardiac injury.
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