Positive Health Online

Abstract

MERCER and COLLEAGUES, 1. 1 Department of Pediatrics at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; 2. 2 Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA; 3. 3 Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; 4. 4 Department of Pathology at the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA conducted studies to characterize liver tumour promotion in a model of non-alcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol.

Background

Alcoholic and non-alcoholic fatty liver diseases 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 reduced tumour promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumour promotion including inflammation, sphingolipid signalling, and Wnt/β-catenin signalling. The authors have extended these studies to characterize liver tumor promotion in a model of non-alcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol.

Methodology

Mice treated with diethylnitrosamine 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.

Results

Relative to mice fed normal chow, a high fat/casein diet led to increased tumour promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signalling in this non-alcoholic fatty liver disease model.

Conclusion

We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein source on hepatic tumor promotion in a mouse model reflecting aspects of non-alcoholic fatty liver disease (NAFLD). A high-fat liquid diet with casein as the protein source promotes hepatic injury and tumor promotion in diethylnitrosamine-treated mice. Replacing casein with a soy protein isolate led to a pronounced diminishment of tumor promotion and associated hepatic injury and inflammation. The study thus demonstrates that a dietary protein source can have beneficial, preventative effects on hepatic tumor promotion.

References

Mercer KE1,2, Pulliam CF3, Pedersen KB3, Hennings L4, Ronis MJ3. Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet. Exp Biol Med (Maywood). 242(6):635-644. Mar 2017. doi: 10.1177/1535370216685436. Epub Jan 5 2017.