Comparison of 1H-magnetic resonance spectroscopy and blood biochemistry as methods for monitoring non-diffuse hepatic steatosis in a rat model.

Abstract

No method of monitoring drug-induced hepatic steatosis has been established, which is a concern in drug development. Hepatic steatosis is divided into diffuse and non-diffuse forms according to the pattern of fat deposition. Diffuse hepatic steatosis was reported as evaluable by 1H-magnetic resonance spectroscopy (1H-MRS), which is used as an adjunct to the MRI examination. Blood biomarkers for hepatic steatosis have been also actively investigated. However, there are few reports to conduct 1H-MRS or blood test in human or animal non-diffuse hepatic steatosis with reference to histopathology. Therefore, to investigate whether non-diffuse hepatic steatosis can be monitored by 1H-MRS and/or blood samples, we compared histopathology to 1H-MRS and blood biochemistry in a non-diffuse hepatic steatosis rat model. Non-diffuse hepatic steatosis was induced by feeding rats the methionine choline deficient diet (MCDD) for 15 days. The evaluation sites of 1H-MRS and histopathological examination were three hepatic lobes in each animal. The hepatic fat fraction (HFF) and the hepatic fat area ratio (HFAR) were calculated from 1H-MRS spectra and digital histopathological images, respectively. Blood biochemistry analyses included triglycerides, total cholesterol, alanine aminotransferase, and aspartate aminotransferase. A strong correlation was found between HFFs and HFARs in each hepatic lobe (r=0.78, p<0.0001) in rats fed the MCDD. On the other hand, no correlation was found between blood biochemistry values and HFARs. This study showed that 1H-MRS parameters correlated with histopathological changes but blood biochemistry parameters didn't, so that it is suggested that 1H-MRS has the potential to be a monitoring method for non-diffuse hepatic steatosis in rats fed the MCDD. Given that 1H-MRS is commonly used in preclinical and clinical studies, 1H-MRS should be considered a candidate method for monitoring drug-induced hepatic steatosis.