Dataset Information

Temporal metabolic profiling of plasma during endotoxemia in humans.

ABSTRACT: Endotoxemia induced by the administration of low-dose lipopolysaccharide (LPS) to healthy human volunteers is a well-established experimental protocol and has served as a reproducible platform for investigating the responses to systemic inflammation. Because metabolic composition of a tissue or body fluid is uniquely altered by stimuli and provides information about the dominant regulatory mechanisms at various cellular processes, understanding the global metabolic response to systemic inflammation constitutes a major part in this investigation complementing the studies undertaken so far in both clinical and systems biology fields. This article communicates the first proof-of-principle metabonomic analysis, which comprised global biochemical profiles in human plasma samples from healthy subjects given intravenous endotoxin at 2 ng/kg. Concentrations of a total of 366 plasma biochemicals were determined in archived blood samples collected from 15 endotoxin-treated subjects at five time points within 24 h after treatment and compared with control samples collected from four saline-treated subjects. Principal component analysis within this data set determined the sixth hour as a critical time point separating development and recovery phases of the LPS-induced metabolic changes. Consensus clustering of the differential metabolites identified two distinct subsets of metabolites that displayed common coherent profiles with opposing directionality. The first group of metabolites, which were mostly associated with pathways related to lipid metabolism, was upregulated within the first 6 h and downregulated by the 24th hour following LPS administration. The second group of metabolites, in contrast, was first downregulated until the sixth hour, then upregulated. Metabolites in this group were predominantly amino acids or their derivatives. In summary, nontargeted biochemical profiling and unsupervised multivariate analyses highlighted the prominent roles of lipid and protein metabolism in regulating the response to systemic inflammation while also revealing their dynamics in opposite directions.

SUBMITTER: Kamisoglu K

PROVIDER: S-EPMC3970546 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Temporal metabolic profiling of plasma during endotoxemia in humans.

Kamisoglu Kubra K Sleight Kirsten E KE Calvano Steve E SE Coyle Susette M SM Corbett Siobhan A SA Androulakis Ioannis P IP

Shock (Augusta, Ga.) 20131201 6

Endotoxemia induced by the administration of low-dose lipopolysaccharide (LPS) to healthy human volunteers is a well-established experimental protocol and has served as a reproducible platform for investigating the responses to systemic inflammation. Because metabolic composition of a tissue or body fluid is uniquely altered by stimuli and provides information about the dominant regulatory mechanisms at various cellular processes, understanding the global metabolic response to systemic inflammat ...[more]

PMID: 24089011

Similar Datasets

Project description:Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disorder that is implicated in dysregulations in multiple biological pathways, orchestrated by interactions between genetic predisposition, metabolic syndromes and environmental factors. The limited knowledge of its pathogenesis is one of the bottlenecks in the development of prognostic and therapeutic options for MAFLD. Moreover, the extent to which metabolic pathways are altered due to ongoing hepatic steatosis, inflammation and fibrosis and subsequent liver damage remains unclear. To uncover potential MAFLD pathogenesis in humans, we employed an untargeted nuclear magnetic resonance (NMR) spectroscopy- and high-resolution mass spectrometry (HRMS)-based multiplatform approach combined with a computational multiblock omics framework to characterize the plasma metabolomes and lipidomes of obese patients without (n = 19) or with liver biopsy confirmed MAFLD (n = 63). Metabolite features associated with MAFLD were identified using a metabolome-wide association study pipeline that tested for the relationships between feature responses and MAFLD. A metabolic pathway enrichment analysis revealed 16 pathways associated with MAFLD and highlighted pathway changes, including amino acid metabolism, bile acid metabolism, carnitine shuttle, fatty acid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and steroid metabolism. These results suggested that there were alterations in energy metabolism, specifically amino acid and lipid metabolism, and pointed to the pathways being implicated in alerted liver function, mitochondrial dysfunctions and immune system disorders, which have previously been linked to MAFLD in human and animal studies. Together, this study revealed specific metabolic alterations associated with MAFLD and supported the idea that MAFLD is fundamentally a metabolism-related disorder, thereby providing new perspectives for diagnostic and therapeutic strategies.

Dataset Information

Temporal metabolic profiling of plasma during endotoxemia in humans.

Publications

Temporal metabolic profiling of plasma during endotoxemia in humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets