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

被引:25
作者
Griffitts, J. [1 ,2 ]
Tesiram, Y. [1 ]
Reid, G. E. [3 ,4 ]
Saunders, D. [1 ]
Floyd, R. A.
Towner, R. A. [1 ,2 ]
机构
[1] Oklahoma Med Res Fdn, Adv Magnet Resonance Ctr, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA
[3] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA
[4] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA
基金
美国国家卫生研究院;
关键词
unsaturated fatty acids; tumor lipid metabolism; liver cancer; magnetic resonance spectroscopy; mice; RAT HEPATOCARCINOGENESIS; GENE-EXPRESSION; PROSTATE-CANCER; SPECTROSCOPY; ACIDS; LIPIDS; QUANTITATION; IONIZATION; THERAPY; TISSUES;
D O I
10.1194/jlr.M800265-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 TGF alpha/c-myc mouse hepatocellular carcinoma (HCC) model. HPLC analysis of the TGF alpha/c-myc mice liver tissue revealed a significant increase in the amount of oleic acid, along with alterations in linoleic and gamma-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 TGF alpha/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.-Griffitts, J., Y. Tesiram, G. E. Reid, D. Saunders, R. A. Floyd, and R. A. Towner. In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGFa/c-myc transgenic mouse model. J. Lipid Res. 2009. 50: 611-622.
引用
收藏
页码:611 / 622
页数:12
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