Immunomodulatory activity of hyaluronidase is associated with metabolic adaptations during acute inflammation

Pereira, Priscilla Aparecida Tártari; Bitencourt, Claudia S.; Reis, Mouzarllem Barros; Frantz, Fabiani Gai; Sorgi, Carlos Artério; Souza, Camila Oliveira Silva; Silva, Célio Lopes; Gardinassi, Luiz Gustavo; Faccioli, Lúcia Helena

doi:10.1007/s00011-019-01297-x

Cited by 13 publications

(9 citation statements)

References 43 publications

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“…Our detailed pathway analysis results showed that FGF19 pretreatment suppressed USFA biosynthesis and LA and GLA were involved. Peritoneal fluid metabolomics or serum metabolomics revealed that LA level was increased in rodent treated by LPS, and biosynthesis of USFA was influenced [ 39 , 40 ]. In agreement with these previous study, LPS increased LA, GLA, DGLA, and DHA.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice

Liu

Tang

Cui

et al. 2022

Oxidative Medicine and Cellular Longevity

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Sepsis is extremely heterogeneous pathology characterized by complex metabolic changes. Fibroblast growth factor 19 (FGF19) is a well-known intestine-derived inhibitor of bile acid biosynthesis. However, it is largely unknown about the roles of FGF19 in improving sepsis-associated metabolic disorder and organ injury. In the present study, mice were intravenously injected recombinant human FGF19 daily for 7 days followed by lipopolysaccharide (LPS) administration. At 24 hours after LPS stimuli, sera were collected for metabolomic analysis. Ingenuity pathway analysis (IPA) network based on differential metabolites (DMs) was conducted. Here, metabolomic analysis revealed that FGF19 pretreatment reversed the increase of LPS-induced fatty acids. IPA network indicated that altered linoleic acid (LA) and gamma-linolenic acid (GLA) were involved in the regulation of oxidative stress and mitochondrial function and were closely related to reactive oxygen species (ROS) generation. Further investigation proved that FGF19 pretreatment decreased serum malondialdehyde (MDA) levels and increased serum catalase (CAT) levels. In livers, FGF19 suppressed the expression of inducible NO synthase (iNOS) and enhanced the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and hemeoxygenase-1 (HO-1). Finally, FGF19 pretreatment protected mice against LPS-induced liver, ileum, and kidney injury. Taken together, FGF19 alleviates LPS-induced organ injury associated with improved serum LA and GLA levels and oxidative stress, suggesting that FGF19 might be a promising target for metabolic therapy for sepsis.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice

Liu

Tang

Cui

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Protective activation of HYAL enzymes has been also demonstrated by decreasing the expression of TNF-α and IL-6 29 . A recent study has shown that HYAL suppressed neutrophil recruitment and cytokine production in a murine model of acute inflammation 30 . However, the immunoregulatory functions of HYAL-1 are contradictory.…”

Section: Discussionmentioning

confidence: 99%

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea

Mészáros

Kis

Kunos

et al. 2020

Sci Rep

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Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31–0.88/ng/mL vs. 0.31/0.31–0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11–59.25/ng/mL vs. 46.83/25.41–89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = − 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA.

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“…Untargeted metabolomics data was performed with full scan mass spectral data acquired in positive mode, with mass-to-charge ratio ( m/z ) ranging from 100 - 1500, as previously described [26]. The package apLCMS [27] was used for peak peaking, noise filtering, retention time and m/z alignment, and feature quantification.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Profile in Plasma and CSF of Levodopa-Induced Dyskinesia of Parkinson’s Disease

Gardinassi

Bortolanza

et al. 2020

Preprint

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Structured AbstractBackgroundThe existence of few biomarkers and the lack of a better understanding of the pathophysiology of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD) require new approaches, as the metabolomic analysis, for discoveries.ObjectivesWe aimed to identify a metabolic profile associated with LID in patients with PD in an original cohort, and to confirm the results in an external cohort (BioFIND).MethodsIn the original cohort, plasma and CSF were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. LC-MS/MS and metabolomics data analysis were used to perform untargeted metabolomics. Untargeted metabolomics data from the BioFIND cohort were analyzed.ResultsWe identified a metabolic profile associated with LID in PD, composed of multiple metabolic pathways. In particular, the dysregulation of glycosphingolipids metabolic pathway was more related to LID and was strongly associated with the severity of dyskinetic movements. Further, bile acid biosynthesis and C21-steroid hormone biosynthesis metabolites simultaneously found in plasma and CSF have distinguished patients with LID from other participants. Levels of cortisol and cortisone were reduced in patients with PD and LID compared to patients with PD without LID. Data from the BioFIND cohort confirmed dysregulation in plasma metabolites from the bile acid biosynthesis and C21-steroid hormone biosynthesis pathways.ConclusionThere is a distinct metabolic profile associated with LID in PD, both in plasma and CSF, which may be associated with the dysregulation of lipid metabolism and neuroinflammation.

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Immunomodulatory activity of hyaluronidase is associated with metabolic adaptations during acute inflammation

Cited by 13 publications

References 43 publications

Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice

Fibroblast Growth Factor 19 Improves LPS-Induced Lipid Disorder and Organ Injury by Regulating Metabolomic Characteristics in Mice

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea

Metabolic Profile in Plasma and CSF of Levodopa-Induced Dyskinesia of Parkinson’s Disease

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