Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver Lipidomics

Abstract

Background: The aim of this study was to characterize the disorder of lipid metabolism in hepatocellular carcinoma (HCC). HCC is a worldwide disease. The research into the disorder of lipid metabolism in HCC is very limited. Study of lipid metabolism in liver cancer tissue may have the potential to provide new insight into HCC mechanisms. Methods: A lipidomics study of HCC based on Ultra high performance liquid chromatography-electronic spray ionization-QTOF mass spectrometer (UPLC-ESI-QTOF MS) and Matrix assisted laser desorption ionization-fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS) was performed. Results: Triacylglycerols (TAGs) with the number of double bond (DB) > 2 (except 56:5 and 56:4 TAG) were significantly down-regulated; conversely, others (except 52:2 TAG) were greatly up-regulated in HCC tissues. Moreover, the more serious the disease was, the higher the saturated TAG concentration and the lower the polyunsaturated TAG concentration were in HCC tissues. The phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) were altered in a certain way. Sphingomyelin (SM) was up-regulated and ceramide (Cer) were down-regulated in HCC tissues. Conclusions: To our knowledge, this is the first such report showing a unique trend of TAG, PC, PE and PI. The use of polyunsaturated fatty acids, like eicosapentanoic and docosahexanoic acid, as supplementation, proposed for the treatment of Non-alcoholic steatohepatitis (NASH), may also be effective for the treatment of HCC.

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

“…Similarly, we found a range of further altered cancer metabolic pathways, from fatty acids to nucleotides and proteinogenic amino acids [58]. The increase of these fatty acids in HCC tissues compared to paired non-malignant hepatic tissues is consistent with earlier studies [59][60][61], confirming aberrant lipid metabolism in HCC tissues. Fatty acids are important for cancer cell proliferation [62].…”

Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma

“…Moreover, they described higher hepatic levels of six TAGs, one sphingomyelin (SM), and one ceramide (CM). In contrast, two works reported an important reduction of CM levels in HCC tissues with a concomitant increase of SMs [ 153 , 158 ]. This underlines an impaired activity of sphingomyelinase with a consequent lower conversion of SM to ceramide.…”

Sphingolipids in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma: Ceramide Turnover

“…Although there is a ceramide increase during NAFLD development at all the stages [76,77,89], ceramide content has been reported to be reduced in HCC leading to a decrease in apoptosis [116] that correlates with the highly proliferative capacity of the disease [117]. Such reduction is caused by the metabolism of ceramide into other bioactive compounds.…”