PMID- 35269702
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20230308
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 5
DP  - 2022 Feb 25
TI  - Imbalances in TCA, Short Fatty Acids and One-Carbon Metabolisms as Important 
      Features of Homeostatic Disruption Evidenced by a Multi-Omics Integrative 
      Approach of LPS-Induced Chronic Inflammation in Male Wistar Rats.
LID - 10.3390/ijms23052563 [doi]
LID - 2563
AB  - 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-alpha) 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, beta-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.
FAU - Hernandez-Baixauli, Julia
AU  - Hernandez-Baixauli J
AUID- ORCID: 0000-0002-9166-4173
AD  - Eurecat, Centre Tecnologic de Catalunya, Unitat de Nutricio i Salut, 43204 Reus, 
      Spain.
FAU - Abasolo, Nerea
AU  - Abasolo N
AD  - Eurecat, Centre Tecnologic de Catalunya, Centre for Omic Sciences (COS), Joint 
      Unit Universitat Rovira i Virgili-EURECAT, 43204 Reus, Spain.
FAU - Palacios-Jordan, Hector
AU  - Palacios-Jordan H
AUID- ORCID: 0000-0002-8628-0765
AD  - Eurecat, Centre Tecnologic de Catalunya, Centre for Omic Sciences (COS), Joint 
      Unit Universitat Rovira i Virgili-EURECAT, 43204 Reus, Spain.
FAU - Foguet-Romero, Elisabet
AU  - Foguet-Romero E
AD  - Eurecat, Centre Tecnologic de Catalunya, Centre for Omic Sciences (COS), Joint 
      Unit Universitat Rovira i Virgili-EURECAT, 43204 Reus, Spain.
FAU - Sunol, David
AU  - Sunol D
AD  - Eurecat, Centre Tecnologic de Catalunya, Digital Health, 08005 Barcelona, Spain.
FAU - Galofre, Mar
AU  - Galofre M
AD  - Eurecat, Centre Tecnologic de Catalunya, Digital Health, 08005 Barcelona, Spain.
FAU - Caimari, Antoni
AU  - Caimari A
AUID- ORCID: 0000-0001-6144-0294
AD  - Eurecat, Centre Tecnologic de Catalunya, Unitat de Nutricio i Salut, 43204 Reus, 
      Spain.
FAU - Baselga-Escudero, Laura
AU  - Baselga-Escudero L
AD  - Eurecat, Centre Tecnologic de Catalunya, Unitat de Nutricio i Salut, 43204 Reus, 
      Spain.
FAU - Del Bas, Josep M
AU  - Del Bas JM
AUID- ORCID: 0000-0002-0700-2004
AD  - Eurecat, Centre Tecnologic de Catalunya, Unitat de Nutricio i Salut, 43204 Reus, 
      Spain.
FAU - Mulero, Miquel
AU  - Mulero M
AUID- ORCID: 0000-0003-2545-2065
AD  - Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 
      Tarragona, Spain.
AD  - Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, 
      Universitat Rovira i Virgili, 43007 Tarragona, Spain.
LA  - eng
GR  - PRIV2019-PREVENTOMICS/Accio-Eurecat/
GR  - TECNOMIFOOD project. CER-20191010./Spanish Ministry of Science and Innovation/
PT  - Journal Article
DEP - 20220225
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Fatty Acids)
RN  - 0 (Lipopolysaccharides)
RN  - 7440-44-0 (Carbon)
SB  - IM
MH  - Animals
MH  - Carbon
MH  - *Fatty Acids
MH  - Homeostasis
MH  - Humans
MH  - Inflammation
MH  - *Lipopolysaccharides/toxicity
MH  - Male
MH  - Metabolome
MH  - Rats
MH  - Rats, Wistar
PMC - PMC8910732
OTO - NOTNLM
OT  - biomarker
OT  - chronic inflammation
OT  - energy metabolism
OT  - lipopolysaccharide
OT  - metabolome
OT  - microbiome
OT  - mitochondria
OT  - one-carbon metabolism
COIS- The authors declare no conflict of interest.
EDAT- 2022/03/11 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/02/25
CRDT- 2022/03/10 15:35
PHST- 2021/12/21 00:00 [received]
PHST- 2022/02/21 00:00 [revised]
PHST- 2022/02/23 00:00 [accepted]
PHST- 2022/03/10 15:35 [entrez]
PHST- 2022/03/11 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/02/25 00:00 [pmc-release]
AID - ijms23052563 [pii]
AID - ijms-23-02563 [pii]
AID - 10.3390/ijms23052563 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Feb 25;23(5):2563. doi: 10.3390/ijms23052563.