1H and 13C NMR studies of tissue from normal and diseased mice. Analysis of T1 and T2 relaxation profiles of triglycerides in liver.

Abstract

The study was initiated to gain a better understanding of the manifestation of disease in the lipid dynamics in tissue. We have performed high resolution 13C and 1H NMR relaxation measurements on the observable lipid resonances in liver and adipose tissue, excised from mice which were normal fed, normal fasted, and infected with the malarial parasite Plasmodium berghei. We have observed that, although the parasite does not invade the hepatocytes, the composition of the liver lipids changes along with nutritional status and disease state. Analysis of the liver lipids using gas chromatography showed that in all cases studied (normal or malarial, fed or fasted) the phospholipid content of the liver remains constant. The triglyceride content, however, shows an increase of up to fourfold in both 24-hour fasted controls and highly parasitized mice. The fatty acid compositions of the triglycerides in 24-hour fasted normal and highly parasitized mice are altered, when compared with fed controls or with mice having a low level of infection. The unsaturation index increases twofold. The 13C T1 experiments on the methylene and olefinic resonances of liver give a single exponential decay. The value for a particular carbon is independent of the origin of the tissue, the nutritional status or the disease state of the animal. In contrast, both 1H and 13C T2 relaxation of the methylene and olefinic carbon resonances can generally be best analyzed as the sum of two exponential decays (based on an F-test). The 13C T2 values and the pre-exponential weighting factors are independent of the origin of the tissue examined. The T2 data could also be analyzed in terms of a distribution of relaxation times, a physically more realistic model. Lastly, our results suggest that the 1H and 13C resonances of lipids in the cells of diseased or normal liver tissues do not give rise to "long" T2 values, as have been observed in cancer cells with metastatic potential.