In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGFα/c-myc transgenic mouse model

• Published in: Journal of lipid research Vol. 50; no. 4; pp. 611 - 622
• Main Authors: Griffitts, J., Tesiram, Y., Reid, G.E., Saunders, D., Floyd, R.A., Towner, R.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2009; American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: Animals; Blotting, Western; Chromatography, High Pressure Liquid; Fatty Acids, Unsaturated - chemistry; Fatty Acids, Unsaturated - metabolism; Genes, myc; liver cancer; Liver Neoplasms, Experimental - genetics; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - pathology; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Transgenic; Oligonucleotide Array Sequence Analysis; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Transforming Growth Factor alpha - genetics; tumor lipid metabolism; unsaturated fatty acids; magnetic resonance spectroscopy; liver cancer; unsaturated fatty acids; tumor lipid metabolism; mice
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M800265-JLR200

Current detection methods (computed tomography, ultrasound, and MRI) for hepatocarcinogenesis in humans rely on visual confirmation of neoplastic formations. A more effective early detection method is needed. Using in vivo magnetic resonance spectroscopy (MRS), we show that alterations in the integral ratios of the bis-allyl to vinyl hydrogen protons in unsaturated lipid fatty acyl groups correlate with the development of neoplastic formations in vivo in a TGFα/c-myc mouse hepatocellular carcinoma (HCC) model. HPLC analysis of the TGFα/c-myc mice liver tissue revealed a significant increase in the amount of oleic acid, along with alterations in linoleic and γ-linolenic acids, as compared with control CD1 mice. Electrospray ionization tandem mass spectrometry analysis indicated a significant increase in the abundance of specific glycerol phosphatidylcholine (GPCho) lipids containing palmitic and oleic acids between control CD1 and TGFα/c-myc mice liver tissue extracts. Western blot analysis of the mice liver tissue indicates alterations in the desaturase enzyme stearoyl CoA desaturase (SCD)1, responsible for palmitic and oleic acid formation. Microarray analysis detected alterations in several genes involved with fatty acid metabolism, particularly SCD2, in transgenic mouse liver tissue. In correlation with the HPLC, mass spectrometry, Western blot, and microarray analyses, we are able to confirm the ability of in vivo MRS to detect precancerous lesions in the mouse liver before visual neoplastic formations were detectable by MRI.