scholarly journals Non-esterified Very Long-chain Fatty Acids Are Accumulated in Colorectal Cancer Tissues

2020 ◽  
Author(s):  
Kotaro Hama ◽  
Yuko Fujiwara ◽  
Tamuro Hayama ◽  
Tsuyoshi Ozawa ◽  
Keijiro Nozawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Cultured Cells ◽  
Fatty Acid Transport ◽  
Long Chain Fatty Acids ◽  
Liquid Chromatography Mass Spectrometry ◽  
Precise Diagnosis ◽  
Cancer Tissues ◽  
Long Chain ◽  
Chain Fatty Acids

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) was 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 non-esterified fatty acids, phospholipids and acyl-CoA species by liquid-chromatography–mass spectrometry and showed that VLCFA is accumulated as the non-esterified form in CRC tissues. We also showed that the expression level of elongation of very long-chain fatty acids 1 (ELOVL1) is increased, whereas fatty acid transport protein 4 (FATP4) is decreased in CRC tissues. Finally, we showed that the amount of non-esterified VLCFA species was significantly up-regulated in cultured cells overexpressing ELOVL1. Our results suggest that the upregulation of ELOVL1 and the down-regulation of FATP4 cooperatively lead to the accumulation of non-esterified VLCFA in CRC tissues.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Hama ◽  
Yuko Fujiwara ◽  
Tamuro Hayama ◽  
Tsuyoshi Ozawa ◽  
Keijiro Nozawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Neutral Lipids ◽  
Long Chain Fatty Acids ◽  
Liquid Chromatography Mass Spectrometry ◽  
Nonesterified Fatty Acids ◽  
Precise Diagnosis ◽  
Cancer Tissues ◽  
Long Chain ◽  
Chain Fatty Acids

AbstractColorectal 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.

scholarly journals Evaluating Ultra-long-Chain Fatty Acids as Biomarkers of Colorectal Cancer Risk

2016 ◽  
Vol 25 (8) ◽  
pp. 1216-1223 ◽  
Author(s):  
Kelsi Perttula ◽  
William M.B. Edmands ◽  
Hasmik Grigoryan ◽  
Xiaoming Cai ◽  
Anthony T. Iavarone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Cancer Risk ◽  
Colorectal Cancer Risk ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals Distinct roles of specific fatty acids in cellular processes: implications for interpreting and reporting experiments

2012 ◽  
Vol 302 (1) ◽  
pp. E1-E3 ◽  
Author(s):  
Matthew J. Watt ◽  
Andrew J. Hoy ◽  
Deborah M. Muoio ◽  
Rosalind A. Coleman
Keyword(s):  
Fatty Acids ◽  
High Fat Diet ◽  
Cultured Cells ◽  
Cellular Function ◽  
Long Chain Fatty Acids ◽  
High Fat ◽  
Cellular Processes ◽  
Stress Effects ◽  
Long Chain ◽  
Chain Fatty Acids

Plasma contains a variety of long-chain fatty acids (FAs), such that about 35% are saturated and 65% are unsaturated. There are countless examples that show how different FAs impart specific and unique effects, or even opposing actions, on cellular function. Despite these differing effects, palmitate (C16:0) is regularly used to represent “FAs” in cell based experiments. Although palmitate can be useful to induce and study stress effects in cultured cells, these effects in isolation are not physiologically relevant to dietary manipulations, obesity, or the consequences of physiological concentrations of FAs. Hence, authors should avoid conclusions that generalize about “FAs” or “saturated FAs” or “high-fat diet” effects if only a single FA was used in the reported experiments.

Fuel partitioning and food intake: role for mitochondrial fatty acid transport

1990 ◽  
Vol 258 (1) ◽  
pp. R216-R221 ◽  
Author(s):  
M. I. Friedman ◽  
I. Ramirez ◽  
C. R. Bowden ◽  
M. G. Tordoff
Keyword(s):  
Fatty Acids ◽  
Food Intake ◽  
Metabolic Effects ◽  
Fatty Acid Transport ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Mitochondrial Fatty Acid ◽  
Cpt I ◽  
Long Chain ◽  
Chain Fatty Acids

Administration of methyl palmoxirate (MP; 10 mg/kg po), an inhibitor of carnitine palmitoyltransferase I (CPT I), increased the food intake of rats maintained on a diet high in triglycerides comprised of long-chain fatty acids, which require CPT I for mitochondrial uptake and oxidation. MP did not affect food intake in rats fed a comparable diet high in medium-chain fatty acids, which do not require CPT I for mitochondrial uptake and oxidation. The feeding response to MP was reduced more effectively by an intragastric preload of medium-chain triglyceride (MCT) oil than a preload of a long-chain triglyceride (LCT) oil. Food intake of MCT- and LCT-fed rats differed under control conditions (no MP), and this appeared to reflect differences in the diurnal distribution of feeding. Measurement of plasma ketone body concentrations indicated that the dietary manipulations and MP had their intended metabolic effects. The results strongly suggest that mitochondrial transport of fatty acids plays a role in the control of food intake. CPT I participates in that control by regulating the partitioning of long-chain fatty acids between pathways of storage and intramitochondrial oxidation.

scholarly journals Transmembrane Movement of Exogenous Long-Chain Fatty Acids: Proteins, Enzymes, and Vectorial Esterification

2003 ◽  
Vol 67 (3) ◽  
pp. 454-472 ◽  
Author(s):  
Paul N. Black ◽  
Concetta C. DiRusso
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Molecular Genetics ◽  
Fatty Acyl ◽  
Model Systems ◽  
Fatty Acid Transport ◽  
Long Chain Fatty Acids ◽  
Acid Transport ◽  
Long Chain ◽  
Chain Fatty Acids

SUMMARY The processes that govern the regulated transport of long-chain fatty acids across the plasma membrane are quite distinct compared to counterparts involved in the transport of hydrophilic solutes such as sugars and amino acids. These differences stem from the unique physical and chemical properties of long-chain fatty acids. To date, several distinct classes of proteins have been shown to participate in the transport of exogenous long-chain fatty acids across the membrane. More recent work is consistent with the hypothesis that in addition to the role played by proteins in this process, there is a diffusional component which must also be considered. Central to the development of this hypothesis are the appropriate experimental systems, which can be manipulated using the tools of molecular genetics. Escherichia coli and Saccharomyces cerevisiae are ideally suited as model systems to study this process in that both (i) exhibit saturable long-chain fatty acid transport at low ligand concentrations, (ii) have specific membrane-bound and membrane-associated proteins that are components of the transport apparatus, and (iii) can be easily manipulated using the tools of molecular genetics. In both systems, central players in the process of fatty acid transport are fatty acid transport proteins (FadL or Fat1p) and fatty acyl coenzyme A (CoA) synthetase (FACS; fatty acid CoA ligase [AMP forming] [EC 6.2.1.3]). FACS appears to function in concert with FadL (bacteria) or Fat1p (yeast) in the conversion of the free fatty acid to CoA thioesters concomitant with transport, thereby rendering this process unidirectional. This process of trapping transported fatty acids represents one fundamental mechanism operational in the transport of exogenous fatty acids.

scholarly journals Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPARα-regulated genes

2020 ◽  
Vol 295 (17) ◽  
pp. 5737-5750 ◽  
Author(s):  
Vincent M. Perez ◽  
Jeffrey Gabell ◽  
Mark Behrens ◽  
Nishikant Wase ◽  
Concetta C. DiRusso ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Transport Protein ◽  
Transcriptomic Analysis ◽  
Fatty Acid Transport ◽  
Long Chain Fatty Acids ◽  
Acid Transport ◽  
Fatty Acid Transport Protein ◽  
Long Chain ◽  
Chain Fatty Acids

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.

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