Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study

Abstract

Recent evidence suggests that lipid composition in cancer tissues may undergo multiple alterations. However, no comprehensive analysis of various lipid groups in colorectal cancer (CRC) tissue has been conducted thus far. To address the problem in question, we determined the contents of triacylglycerols (TG), an energetic substrate, various lipids necessary for cell membrane formation, among them phospholipids (phosphatidylcholine, phosphatidylethanolamine), sphingolipids (sphingomyelin) and cholesterol (free, esterified and total), and fatty acids included in complex lipids. 1H-nuclear magnetic resonance (1H-NMR) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the lipid composition of colon cancer tissue and normal large intestinal mucosa from 25 patients. Compared with normal tissue, cancer tissues had significantly lower TG content, along with elevated levels of phospholipids, sphingomyelin, and cholesterol. Moreover, the content of oleic acid, the main component of TG, was decreased in cancer tissues, whereas the levels of saturated fatty acids and polyunsaturated fatty acids (PUFAs), which are principal components of polar lipids, were elevated. These lipidome rearrangements were associated with the overexpression of genes associated with fatty acid oxidation, and the synthesis of phospholipids and cholesterol. These findings suggest that reprogramming of lipid metabolism might occur in CRC tissue, with a shift towards increased utilization of TG for energy production and enhanced synthesis of membrane lipids, necessary for the rapid proliferation of cancer cells.

Very long-chain fatty acids are accumulated in triacylglycerol and nonesterified forms in colorectal cancer tissues

“…Note that TAG species with long chain acyl moieties, such as TAG 18:1-18:1-16:0, which accounted for the majority in the total TAG fraction, were significantly decreased in CRC tissues (Fig. 3A), supporting the previous result that the level of TAG was lower in CRC compared with normal tissues 10 . It has also been shown that the amount of total VLCFA, including esterified and nonesterified forms, was elevated in the sera of patients with CRC 11 .…”

Rearrangements of Blood and Tissue Fatty Acid Profile in Colorectal Cancer - Molecular Mechanism and Diagnostic Potential

“…Some studies indicate that certain FA levels change depending on the stage of disease ( 5 ). Recently, our study confirmed these observations and showed other alterations in the FA profile in colorectal cancer tissue ( 9 ). Fatty acid profile alterations, such as the presence of cerotic acid ( 6 ) and decrease in the concentration of hydroxylated, polyunsaturated ultra-long-chain fatty acids ( 10 ), can also be found in the sera of CRC patients.…”

“…In contrast, in cancer tissue, 18:1 was observed in smaller amounts than those in normal mucosa. Our recent study suggests that this may be due to the high energy requirement of cancer cells during their rapid proliferation; 18:1, which is found in TAG, undergoes intensive β-oxidation as an energy source in CRC cells ( 9 ). We also found lower levels of ALA and a trend toward a decrease in LA.…”

Lipidomic Signatures for Colorectal Cancer Diagnosis and Progression Using UPLC-QTOF-ESI+MS

“…In serum, there were noticeable increases in triglycerides containing C15:0,18:0, 18:1,18:2 and 18:3 [ 53 , 54 ] or decreases in lipids with C22:0, 24:0, 26:0, 30:0 and 18:1 [ 16 ]; and decreases in ultralong chain fatty acids [ 34 ]; increases in endocannabinoids and ceramides, sphingomyelins, eicosanoids [ 8 , 31 , 43 , 46 ], succinate, dimetihylguanosine, adenine, citraconic acid and methylguanosine [ 40 ]. Cerotic acid may also be a novel serum metabolic marker of colorectal malignancies [ 55 ], as well as plasma triacylglycerols [ 56 , 57 ].…”