Location: Arkansas Children's Nutrition CenterTitle: Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet
|MERCER, KELLY - University Of Arkansas|
|PULLIAM, CASEY - Louisiana State University|
|BRINT, KIM - Louisiana State University|
|HENNINGS, LEAH - University Of Arkansas|
|RONIS, MARTIN - Louisiana State University|
Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2016
Publication Date: 3/2/2017
Citation: Mercer, K., Pulliam, C.F., Brint, K., Hennings, L., Ronis, M.J. 2017. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet. Experimental Biology and Medicine. 242(6):635-644. doi:10.1177/1535370216685436.
Interpretive Summary: Nonalcoholic fatty liver disease (NAFLD) is the leading risk factor for liver cancers, and NAFLD is more prevalent in persons with obesity. Current clinical and animal studies show that both high-quality nutrition weight loss can ameliorate NAFLD, but the specific dietary components that prevent or reduce NAFLD remain to be determined. It is suggested that diets that contain more soy-based foods may prevent liver injury associated with high fat diets, and therefore would potentially lower cancer risk associated with NAFLD. In this study, we tested the hypothesis that a high fat diet supplemented with soy could prevent liver injury and subsequent tumor development, using a mouse model. Male mice treated with a liver carcinogen, diethylnitrosamine, received a high fat liquid diet (HF) composed of either casein or soy protein for 16 weeks. In contrast to the HF/casein diet, the HF/soy diet significantly decreased the presence of tumors in response to diethylnitrosamine. The high-fat diets resulted in a general increase in transcripts for liver cell Wnt/ß-catenin pathway components, factors believed to be an important mechanism whereby these diets stimulate tumorigenesis. Interestingly, soy supplementation did not block Wnt signaling in this model, suggesting that the effect of soy to reduce tumor growth is through alternative mechanisms. These findings support the idea that dietary intervention strategies can lower liver cancer risk in those populations having multiple risk factors including NAFLD.
Technical Abstract: Alcoholic and nonalcoholic fatty liver disease are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate (SPI) reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat-ethanol liquid diet following initiation with diethylnitrosamine (DEN). Feeding SPI inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/B-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic steatohepatitis (NASH) produced by chronic feeding of high-fat diets in the absence of ethanol. Mice treated with DEN on postnatal day 14 were fed a high fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high-fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, inflammation, and sphingolipid signaling. Replacing casein with SPI counteracted these effects. However, SPI did not block Wnt signaling in this NASH model. We conclude that replacing casein with SPI blocks development of steatohepatitis and tumor promotion in DEN-treated mice fed high fat diets.