Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

Li, Shangfu; Gao, Dan; Jiang, Yuyang

doi:10.3390/metabo9020036

Cited by 112 publications

(105 citation statements)

References 137 publications

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“…Particularly, two studies showed higher levels of long-chain acylcarnitines and lower levels of medium and short-chain acyl-carnitines in HCC and serum of patients [ 154 , 161 ]. Acylcarnitine plays a central role in cellular lipid metabolism, as it is involved in the transport of activated LCFAs into mitochondria to sustain FAO [ 162 ]. The authors explain that the high ratio long-chain acylcarnitine/short-chain acylcarnitine is likely due to the high request of β-oxidation [ 154 ].…”

Section: Lipid Metabolic Reprogrammingmentioning

confidence: 99%

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma

Sangineto

Villani

Cavallone

et al. 2020

Cancers

107

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Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, β-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death.

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Section: Lipid Metabolic Reprogrammingmentioning

confidence: 99%

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma

Sangineto

Villani

Cavallone

et al. 2020

Cancers

107

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“…The present study shows that NAGLU −/− mice had increased levels of BCAAs (Leu, Ile, and Val), Phe and Tyr amino acids, free carnitine, and acylcarnitines in both liver and heart tissue. The augmented levels of BCAAs concomitant with the accumulation of short-chain acylcarnitines (C3, C5), involved in BCAA metabolism [33,34], suggest an impaired catabolism of BCAAs in the liver and heart of MPS IIIB-affected mice. BCAA metabolism occurs in the liver; however, it is also active in other tissues, including the heart, adipose tissues, kidney, and skeletal muscle [35].…”

Section: Discussionmentioning

confidence: 99%

Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism

Pasquale

Caterino

Costanzo

et al. 2020

IJMS

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Mucopolysaccharidoses (MPSs) are inherited disorders of the glycosaminoglycan (GAG) metabolism. The defective digestion of GAGs within the intralysosomal compartment of affected patients leads to a broad spectrum of clinical manifestations ranging from cardiovascular disease to neurological impairment. The molecular mechanisms underlying the progression of the disease downstream of the genetic mutation of genes encoding for lysosomal enzymes still remain unclear. Here, we applied a targeted metabolomic approach to a mouse model of PS IIIB, using a platform dedicated to the diagnosis of inherited metabolic disorders, in order to identify amino acid and fatty acid metabolic pathway alterations or the manifestations of other metabolic phenotypes. Our analysis highlighted an increase in the levels of branched-chain amino acids (BCAAs: Val, Ile, and Leu), aromatic amino acids (Tyr and Phe), free carnitine, and acylcarnitines in the liver and heart tissues of MPS IIIB mice as compared to the wild type (WT). Moreover, Ala, Met, Glu, Gly, Arg, Orn, and Cit amino acids were also found upregulated in the liver of MPS IIIB mice. These findings show a specific impairment of the BCAA and fatty acid catabolism in the heart of MPS IIIB mice. In the liver of affected mice, the glucose-alanine cycle and urea cycle resulted in being altered alongside a deregulation of the BCAA metabolism. Thus, our data demonstrate that an accumulation of BCAAs occurs secondary to lysosomal GAG storage, in both the liver and the heart of MPS IIIB mice. Since BCAAs regulate the biogenesis of lysosomes and autophagy mechanisms through mTOR signaling, impacting on lipid metabolism, this condition might contribute to the progression of the MPS IIIB disease.

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“…Carnitine also has an antioxidant and anti-inflammatory capacity [48,50]. Some studies have reported that acetyl-carnitine and carnitine are associated with liver function, liver diseases, neurologic disorders, and IBD [22,[51][52][53][54]. Therefore, liver damage due to intestinal inflammation occurs as a result of changes in the concentrations of acetyl-carnitine and carnitine.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of the Liver of a Dextran Sodium Sulfate-Induced Acute Colitis Mouse Model: Implications of the Gut–Liver Connection

Kim

Lee

Kwon

et al. 2020

Cells

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The incidence of ulcerative colitis (UC) is increasing worldwide, and it has become a growing problem in Asia. Previous research on UC has focused on serum, plasma, urine, gut tissues, and fecal metabolic profiling, but a comprehensive investigation into the correlation between the severity of colitis and changes in liver metabolism is still lacking. Since the liver and gut exchange nutrients and metabolites through a complex network, intestinal diseases can affect both the liver and other organs. In the present study, concentration-dependent dextran sodium sulfate (DSS)-induced ulcerative colitis was employed to examine changes in liver metabolism using a proton nuclear magnetic resonance spectroscopy (1H-NMR)-and ultra-performance liquid chromatography time of flight mass spectroscopy (UPLC-TOF MS)-based metabolomics study. Using the multivariate statistical analysis method orthogonal projections to latent structures discriminant analysis (OPLS-DA), changes in metabolites depending on the DSS dose could be clearly distinguished. Specifically, hepatic metabolites involved in one-carbon metabolism, carnitine-related metabolism, and nucleotide synthesis were found to be affected by intestinal inflammation, implying the existence of a metabolic connection between the gut and liver. We are currently investigating the significance of this metabolic condition in UC.

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Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma

Cited by 112 publications

References 137 publications

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma

Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism

Metabolomic Analysis of the Liver of a Dextran Sodium Sulfate-Induced Acute Colitis Mouse Model: Implications of the Gut–Liver Connection

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