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

https://doi.org/10.1194/jlr.M800265-JLR200Get rights and content
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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.

unsaturated fatty acids
tumor lipid metabolism
liver cancer
magnetic resonance spectroscopy
mice

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Abbreviations

  1. CSI, chemical shift imaging

  2. DU, degree of unsaturation

  3. FDR, false discovery rate

  4. FADS1, fatty acid desaturase 1

  5. FADS2, fatty acid desaturase 2

  6. GPCho, glycerol phosphatidylcholine

  7. GPE, glycerol phosphatidylethanolamine

  8. HCC, hepatocellular carcinoma

  9. MRS, magnetic resonance spectroscopy

  10. PC, phosphatidylcholine

  11. PE, phosphatidylethanolamine

  12. PI, precursor ion

  13. ROI, region of interest

  14. SCD, stearoyl CoA desaturase

  15. TE, echo time

  16. TR, relaxation time

Published, JLR Papers in Press, December 8, 2008.

*

Support for the studies was provided by funding from the Oklahoma Medical Research, the Oklahoma Center for the Advancement of Sciences and Technology (OCAST), grant of fMRI-2, Molecular Image Inc. (Menlo Park, CA), and National Institutes of Health grant RO1CA82506.