Dataset Information

Swine Inflammation and Necrosis Syndrome Is Associated with Plasma Metabolites and Liver Transcriptome in Affected Piglets.

ABSTRACT: Swine Inflammation and Necrosis Syndrome can lead to severe clinical signs, especially in tails, ears, teats, and claws in pigs. Clinical and histopathological findings in newborn piglets with intact epidermis indicate a primarily endogenous etiology, and microbial-associated molecular patterns (MAMPs), such as lipopolysaccharide (LPS) are assumed to play a central role in the development of the syndrome. We hypothesized that swine inflammation and necrosis syndrome (SINS) is indirectly triggered by gut-derived MAMPs entering the circulatory system via the liver and thereby causing derangements on liver metabolism. To test this hypothesis, metabolomes, candidate genes of the liver and liver transcriptomes of 6 piglets with high-grade clinical signs of SINS (SINS high) were examined and compared with 6 piglets without significant signs of SINS (SINS low). Several hepatic pro-inflammatory genes and genes involved in stress response were induced in piglets of the SINS high group. The most striking finding from hepatic transcript profiling and bioinformatic enrichment was that the most enriched biological processes associated with the approximately 220 genes induced in the liver of the SINS high group were exclusively related to metabolic pathways, such as fatty acid metabolic process. Within the genes (≈390) repressed in the liver of the SINS high group, enriched pathways were ribosome biogenesis, RNA processing, RNA splicing, spliceosome, and RNA transport. The transcriptomic findings were supported by the results of the metabolome analyses. These results provide the first evidence for the induction of an inflammatory process in the liver of piglets suffering from SINS, accompanied by lipid metabolic derangement.

SUBMITTER: Ringseis R

PROVIDER: S-EPMC8001383 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:This study investigated the effects of dietary supplementation with fermented Mao-tai lees (FML) on growth performance, plasma metabolites, and intestinal microbiota and metabolites of weaned piglets. A total of 128 Duroc×Landrace×Yorkshire piglets (28-days old) were randomly assigned to one of four groups, feeding a basal diet (control group), a basal diet supplemented with 2, 4 or 6% FML, respectively, for 42days. The results showed that dietary 4% FML supplementation had higher (p<0.05) average daily gain (ADG) and plasma triglyceride concentration during days 1-14 of the trial than the other FML supplemented groups. In addition, dietary 2 and 4% FML supplementation increased (p<0.05) the ADG during days 15-28 of the trial and plasma total protein concentration on day 42 of the trial compared with the 6% FML supplement. The plasma concentrations of arginine, ethanolamine, histidine, isoleucine, lysine, methionine, proline, taurine, threonine, and tyrosine were increased (p<0.05) in the 4% FML group compared with the other three groups on day 14 of the trial. Dietary supplementation with 2-6% FML decreased (p<0.05) the plasma urea nitrogen concentration on day 14 of the trial and the abundance of Escherichia coli in the colon, and dietary 2 and 4% FML supplementation decreased (p<0.05) the abundance of sulfate-reducing bacteria compared with the control group. In the intestinal contents, a higher concentration of FML (6%) supplementation decreased (p<0.05) the colonic acetate concentration compared with the control and 2% FML groups, while 4% FML supplementation increased (p<0.05) the colonic cadaverine concentration compared with the other three groups. In conclusion, dietary 4% FML supplementation might contribute to the increased amino acids metabolism without affecting the growth performance of weaned piglets. Moreover, dietary 2 and 4% FML supplementation were also beneficial to intestinal health via decreasing the abundances of specific pathogens and increasing the concentrations of microbial metabolites in the gut, which provides the theoretical basis and data support for the application of FML in pigs.

Project description:BackgroundEquine metabolic syndrome (EMS) is a multifactorial pathology gathering insulin resistance, low-grade inflammation and past or chronic laminitis. Among the several molecular mechanisms underlying EMS pathogenesis, increased negative insulin signalling regulation mediated by protein tyrosine phosphatase 1 B (PTP1B) has emerged as a critical axis in the development of liver insulin resistance and general metabolic distress associated to increased ER stress, inflammation and disrupted autophagy. Thus, the use of PTP1B selective inhibitors such as MSI-1436 might be considered as a golden therapeutic tool for the proper management of EMS and associated conditions. Therefore, the present investigation aimed at verifying the clinical efficacy of MSI-1436 systemic administration on liver metabolic balance, insulin sensitivity and inflammatory status in EMS affected horses. Moreover, the impact of MSI-1436 treatment on liver autophagy machinery and associated ER stress in liver tissue has been analysed.MethodsLiver explants isolated from healthy and EMS horses have been treated with MSI-1436 prior to gene and protein expression analysis of main markers mediating ER stress, mitophagy and autophagy. Furthermore, EMS horses have been intravenously treated with a single dose of MSI-1436, and evaluated for their metabolic and inflammatory status.ResultsClinical application of MSI-1436 to EMS horses restored proper adiponectin levels and attenuated the typical hyperinsulinemia and hyperglycemia. Moreover, administration of MSI-1436 further reduced the circulating levels of key pro-inflammatory mediators including IL-1β, TNF-α and TGF-β and triggered the Tregs cells activation. At the molecular level, PTP1B inhibition resulted in a noticeable mitigation of liver ER stress, improvement of mitochondrial dynamics and consequently, a regulation of autophagic response. Similarly, short-term ex vivo treatment of EMS liver explants with trodusquemine (MSI-1436) substantially enhanced autophagy by upregulating the levels of HSC70 and Beclin-1 at both mRNA and protein level. Moreover, the PTP1B inhibitor potentiated mitophagy and associated expression of MFN2 and PINK1. Interestingly, inhibition of PTP1B resulted in potent attenuation of ER stress key mediators' expression namely, CHOP, ATF6, HSPA5 and XBP1.ConclusionPresented findings shed for the first time promising new insights in the development of an MSI-1436-based therapy for proper equine metabolic syndrome intervention and may additionally find potential translational application to human metabolic syndrome treatment.

Dataset Information

Swine Inflammation and Necrosis Syndrome Is Associated with Plasma Metabolites and Liver Transcriptome in Affected Piglets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets