Low fat but not soy protein isolate was an effective intervention to reduce non-alcoholic fatty liver disease progression in C57BL/6J mice: Monitored by a novel quantitative ultrasound (QUS) method

Untreated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) lead to irreversible liver damage. We hypothesized that a low-fat diet (LFD) or a high-fat diet (HFD) with soy protein isolate (SPI) would be an effective intervention to halt or reverse NAFLD progression. To test these hypotheses, we conducted two studies. In the first study, we fed a HFD to 7-week-old C57BL/6J mice to induce NAFLD compared to a LFD (control). Hepatic steatosis was monitored by quantitative ultrasound (QUS) scans (in vivo and ex vivo). Animals were euthanized after 0, 2, 4 and 6 weeks of feeding. In the second study, 7-week-old mice were randomized onto a LFD or HFD with SPI intervention after 4 weeks of feeding HFD. Animals from each group were scanned with QUS and euthanized after 4, 9 and 12 weeks of feeding. Animals fed the HFD developed NAFLD (100%) and NASH (80%) characterized by increased liver weight, lipid accumulation, and histological scores for inflammation by 4 weeks in the first study. In the second study, the LFD ameliorated this NAFLD phenotype after 5 weeks of feeding, however the SPI intervention failed to significantly attenuate NAFLD. QUS parameters were significantly increased with the HFDs (p<0.05) and steatosis grade (p<0.05) and were positively correlated with hepatic lipid concentrations. In conclusion, dietary modification may be effective at reversing NAFLD and NASH at early stages. Furthermore, QUS may become a valuable tool to track hepatic steatosis. Additional studies are needed to further evaluate the effectiveness of these interventions.