Abstract
Chronic inflammation is an important risk factor in a broad variety of physical and mental disorders leading to highly prevalent non-communicable diseases (NCDs). However, there is a need for a deeper understanding of this condition and its progression to the disease state. For this reason, it is important to define metabolic pathways and complementary biomarkers associated with homeostatic disruption in chronic inflammation. To achieve that, male Wistar rats were subjected to intraperitoneal and intermittent injections with saline solution or increasing lipopolysaccharide (LPS) concentrations (0.5, 5 and 7.5 mg/kg) thrice a week for 31 days. Biochemical and inflammatory parameters were measured at the end of the study. To assess the omics profile, GC-qTOF and UHPLC-qTOF were performed to evaluate plasma metabolome; 1H-NMR was used to evaluate urine metabolome; additionally, shotgun metagenomics sequencing was carried out to characterize the cecum microbiome. The chronicity of inflammation in the study was evaluated by the monitoring of monocyte chemoattractant protein-1 (MCP-1) during the different weeks of the experimental process. At the end of the study, together with the increased levels of MCP-1, levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) along with 8-isoprostanes (an indicative of oxidative stress) were significantly increased (p-value < 0.05). The leading features implicated in the current model were tricarboxylic acid (TCA) cycle intermediates (i.e., alpha-ketoglutarate, aconitic acid, malic acid, fumaric acid and succinic acid); lipids such as specific cholesterol esters (ChoEs), lysophospholipids (LPCs) and phosphatidylcholines (PCs); and glycine, as well as N, N-dimethylglycine, which are related to one-carbon (1C) metabolism. These metabolites point towards mitochondrial metabolism through TCA cycle, β-oxidation of fatty acids and 1C metabolism as interconnected pathways that could reveal the metabolic effects of chronic inflammation induced by LPS administration. These results provide deeper knowledge concerning the impact of chronic inflammation on the disruption of metabolic homeostasis.
Highlights
Inflammation is a part of a complex biological process characterized by the activation of immune and non-immune cells that protect the host from bacteria, viruses, toxins and infections, eliminating pathogens and promoting tissue repair and recovery [1]
The stability of inflammation was evaluated during the entire experimental period thanks to the monitorization of monocyte chemoattractant protein-1 (MCP-1) during the second week, the third week and at the end of the study (Figure 1)
The results indicate that MCP-1 was elevated during the entire experimental procedure, indicating a constant effect of the LPS treatment in inflammation
Summary
Inflammation is a part of a complex biological process characterized by the activation of immune and non-immune cells that protect the host from bacteria, viruses, toxins and infections, eliminating pathogens and promoting tissue repair and recovery [1]. Chronic inflammation might be understood as a main risk factor, and, we have a long way to go before achieving full understanding about the role that chronic inflammation plays in disease risk, biological aging and NCDs evolution and mortality [4]. Current research on inflammation has focused on the causes of chronic inflammation, the discovery of inflammation-associated biomarkers and the associations between inflammation and disease. Different studies have shown that current biomarkers of inflammation need complementary information to be applied for the monitoring of chronic inflammation. Monitoring the levels of general biomarkers of inflammation has been shown as a promising strategy for the prediction of morbidity and mortality in cross-sectional and longitudinal studies related to inflammation in aging [6]. Alteration of cytokines (e.g., interleukin-1 (IL-1) and interleukin-6 (IL-6)) was discordant between studies [7,8,9]
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