Liver Metabolic Alterations and Changes in Host Intercompartmental Metabolic Correlation during Progression of Malaria

Sengupta, Arjun; Basant, Angika; Ghosh, Soumita; Sharma, Shobhona; Sonawat, Haripalsingh M.

doi:10.1155/2011/901854

Cited by 13 publications

(10 citation statements)

References 24 publications

(43 reference statements)

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“…Metabolomic studies have been reported that are of relevance to Wilson's disease [103, 104], primary biliary cirrhosis [105], primary sclerosing cholangitis [105], the hepatic stage of malaria [106–108], as well as various aspects of hepatic encephalopathy [109–112]. …”

Section: The Metabolomic Window Into Other Hepatobiliary Diseasesmentioning

confidence: 99%

The metabolomic window into hepatobiliary disease

Beyoğlu¹,

Idle²

2013

Journal of Hepatology

202

198

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Summary The emergent discipline of metabolomics has attracted considerable research effort in hepatology. Here we review the metabolomic data for nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), alcoholic liver disease (ALD), hepatitis B and C, cholecystitis, cholestasis, liver transplantation and acute hepatotoxicity in animal models. A metabolomic window has permitted a view into the changing biochemistry occurring in the transitional phases between a healthy liver and hepatocellular carcinoma or cholangiocarcinoma. Whether provoked by obesity and diabetes, alcohol use or oncogenic viruses, the liver develops a core metabolomic phenotype (CMP) that involves dysregulation of bile acid and phospholipid homeostasis. The CMP commences at the transition between the healthy liver (Phase 0) and NAFLD/NASH, ALD or viral hepatitis (Phase 1). This CMP is maintained in the presence or absence of cirrhosis (Phase 2) and whether or not either HCC or CCA (Phase 3) develop. Inflammatory signalling in the liver triggers the appearance of the CMP. Many other metabolomic markers distinguish between Phases 0, 1, 2 and 3. A metabolic remodelling in HCC has been described but metabolomic data from all four Phases demonstrate that the Warburg shift from mitochondrial respiration to cytosolic glycolysis foreshadows HCC and may occur as early as Phase 1. The metabolic remodelling also involves an upregulation of fatty acid β-oxidation, also beginning in Phase 1. The storage of triglycerides in fatty liver provides high energy-yielding substrates for Phases 2 and 3 of liver pathology. The metabolomic window into hepatobiliary disease sheds new light on the systems pathology of the liver.

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Section: The Metabolomic Window Into Other Hepatobiliary Diseasesmentioning

confidence: 99%

The metabolomic window into hepatobiliary disease

Beyoğlu¹,

Idle²

2013

Journal of Hepatology

202

198

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“…Malarial infection was shown to heavily alter peripheral and tissue level metabolite levels [16][17][18][19][20][21][22][23][24][25][26] These studies are carried out after the infections are well established, but alterations in rodent host metabolism during low parasitemia (<1%) are unknown. In RBC cultures at~5% parasitemia, significant alterations in glucose utilization have been observed [14,27], and thus it was of interest to study whether glucose utilization will be affected in the RBCs, liver, and brain of the host during this early stage of malarial infection.…”

Section: Nmr Spectroscopy Of Organ and Cellular Extractsmentioning

confidence: 99%

Early Perturbations in Glucose Utilization in Malaria-Infected Murine Erythrocytes, Liver and Brain Observed by Metabolomics

et al. 2020

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Investigation of glucose utilization during an infection is central to the study of energy metabolism. The heavy utilization of glucose by the malaria parasite, and the consequences of this process, have been investigated extensively. However, host glucose utilization during early infection has not been explored to date. In a first attempt, this article investigates the changes in the host glucose utilization in Balb/c mice infected with Plasmodium berghei ANKA using 13C-labeled glucose infusion followed by NMR spectroscopy. The results suggested significant alterations of liver, brain and red blood cell (RBC) glucose utilization during early infection when the parasitemia was <1%. At the pathway level, we observed a decrease in the shunt metabolite 2,3-bisphosphoglycerate in the RBCs. Glycolysis and pathways associated with it, along with fatty acid unsaturation, were altered in the liver. Significant changes were observed in the central carbon metabolic pathways in the brain. These results have implications in understanding the host physiology during early infection and pave the way for detailed flux analysis of the proposed perturbed pathways.

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“…Multiway Principal Component Analysis (MPCA) is used to understand the metabolic correlations between different organs and compartments of the body [31], [32]. Kidney, spleen and serum constitute three different compartments of the body and MPCA gives metabolic correlations that occur across them.…”

Section: Statistical Analyses Of the Datamentioning

confidence: 99%

Metabolic Perturbations of Kidney and Spleen in Murine Cerebral Malaria: 1H NMR-Based Metabolomic Study

et al. 2013

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A significant fraction of global population is under the threat of malaria. Majority of annual death is due to the more complicated form of the infection i.e. the cerebral form, also known as Cerebral Malaria (CM). Host parasite interaction is known to cause a cascade of events in various tissues like brain, liver, kidney, and spleen. We have employed 1H NMR based metabolomics to understand the specific perturbations of various tissues in CM. In our previous paper we have delineated the differences between CM vis-a-vis non-cerebral malaria (NCM) mice in serum, liver and brain. In this paper we focus on their differences of metabolic profile in kidney and spleen as kidney dysfunction and splenomegaly are known to be associated to neurological outcome of the disease. Moreover we have also looked into how the biological compartments (kidney, spleen and serum) interact with each other. The various metabolites involved in such interactions and their correlational aspects across the compartments have been studied in CM, NCM and control mice. The idea was to find out the specific pathways that are altered in CM mice. Our results demonstrate that both the kidney as well as spleen metabolism are differentially perturbed in CM with respect to NCM. The results point out that glutamate levels are decreased in CM mice with respect to NCM mice both in case of spleen and kidney while creatine, myo-inositol and betaine levels are increased in kidney of CM mice with respect to NCM mice. From the analysis of Multiway Principal Component Analysis (MPCA) we see that lipid metabolism and TCA cycle is altered in kidney and spleen.

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Liver Metabolic Alterations and Changes in Host Intercompartmental Metabolic Correlation during Progression of Malaria

Cited by 13 publications

References 24 publications

The metabolomic window into hepatobiliary disease

The metabolomic window into hepatobiliary disease

Early Perturbations in Glucose Utilization in Malaria-Infected Murine Erythrocytes, Liver and Brain Observed by Metabolomics

Metabolic Perturbations of Kidney and Spleen in Murine Cerebral Malaria: 1H NMR-Based Metabolomic Study

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