Abstract
Colorectal cancer (CRC) is a major cancer, and its precise diagnosis is especially important for the development of effective therapeutics. In a series of metabolome analyses, the levels of very long chain fatty acids (VLCFA) were shown to be elevated in CRC tissues, although the endogenous form of VLCFA has not been fully elucidated. In this study we analyzed the amount of nonesterified fatty acids, acyl-CoA species, phospholipids and neutral lipids such as cholesterylesters using liquid-chromatography–mass spectrometry. Here we showed that VLCFA were accumulated in triacylglycerol (TAG) and nonesterified forms in CRC tissues. The levels of TAG species harboring a VLCFA moiety (VLCFA-TAG) were significantly correlated with that of nonesterified VLCFA. We also showed that the expression level of elongation of very long-chain fatty acids protein 1 (ELOVL1) is increased in CRC tissues, and the inhibition of ELOVL1 decreased the levels of VLCFA-TAG and nonesterified VLCFA in CRC cell lines. Our results suggest that the upregulation of ELOVL1 contributes to the accumulation of VLCFA-TAG and nonesterified VLCFA in CRC tissues.
Highlights
Colorectal cancer (CRC) is a major cancer, and its precise diagnosis is especially important for the development of effective therapeutics
A recent cohort study reported that the intake of n-3 polyunsaturated fatty acids (PUFA) reduced the risk of CRC occurrence, whereas the ratio of n-3 PUFA/n-6 PUFA was not correlated with that[2], These results suggested that the pathological contribution of fatty acids and lipid metabolism in CRC remains to be elucidated
These results showed that very long chain fatty acids (VLCFA) species were accumulated in nonesterified form in CRC tissues
Summary
Colorectal cancer (CRC) is a major cancer, and its precise diagnosis is especially important for the development of effective therapeutics. In a series of metabolome analyses, the levels of very long chain fatty acids (VLCFA) were shown to be elevated in CRC tissues, the endogenous form of VLCFA has not been fully elucidated. In this study we analyzed the amount of nonesterified fatty acids, acyl-CoA species, phospholipids and neutral lipids such as cholesterylesters using liquidchromatography–mass spectrometry. Abbreviations ABCD1 ATP-binding cassette transporter subfamily D1 ACSL Acyl-CoA synthetase long-chain family member CE Cholesterylester CRC Colorectal cancer ELOVL Elongation of very long-chain fatty acids protein FATP Fatty acid transport protein FFA Free fatty acid IS Internal standard LC Liquid chromatography MS Mass spectrometry PC Phosphatidylcholine PE Phosphatidylethanolamine PG Phosphatidylglycerol PI Phosphatidylinositol PL Phospholipid PS Phosphatidylserine SM Sphingomyelin TAG Triacylglycerol VLCFA Very long-chain fatty acid. Fatty acyl moieties are liberated from complex lipids during the derivatizing process of sample preparation for GC–MS, leading to loss of information about the VLCFA-containing endogenous lipid species
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