Caloric restriction (CR) and endurance exercise elicit wide-ranging health benefits including reduced risk of select cancers. In addition, diet composition influences oncogenesis, although its interactions with exercise and CR are not well understood. Therefore, to investigate the potential interactions between diet and lifestyle interventions on liver tumorigenesis, the carcinogen diethylnitrosamine was administered to 72 male C57Bl/6 mice that were subsequently fed diets enriched with lard (CTL) or olive oil and were further stratified to voluntary wheel running (Ex) or 30% CR for 49 weeks. Although Ex and diet composition did not influence liver oncogenesis, CR prevented hepatic tumor formation. In addition, CR reduced steatosis, hepatocyte ballooning, inflammation, and immune cell infiltration, all of which are hallmarks in the progression of nonalcoholic fatty liver disease to liver tumorigenesis. RNA sequencing of nontransformed liver tissues from CR mice revealed changes in metabolic pathways and reduced inflammation, cytokine production, stellate cell activation and migration, and genes associated with liver injury and oncogenesis. These data demonstrate that CR protects against steatosis, liver inflammation, and liver injury and is a robust deterrent of carcinogen-induced hepatic oncogenesis..
<p>Fig. S1. Phenotypic and metabolic parameters are influenced by Ex and CR. Fig. S2. CR modulates additional markers of hepatic inflammation and immune cell infiltration. Fig. S3. CR causes divergence of genes in comparison to CTL mice. Fig. S4. CR affects gene signature pathways and networks associated with hepatic inflammation and metabolism. Table S1. Description of components (g/Kg) and macronutrient content (% kcal) of diets.</p>
<div>Abstract<p>Caloric restriction (CR) and endurance exercise elicit wide-ranging health benefits including reduced risk of select cancers. In addition, diet composition influences oncogenesis, although its interactions with exercise and CR are not well understood. Therefore, to investigate the potential interactions between diet and lifestyle interventions on liver tumorigenesis, the carcinogen diethylnitrosamine was administered to 72 male C57Bl/6 mice that were subsequently fed diets enriched with lard (CTL) or olive oil and were further stratified to voluntary wheel running (Ex) or 30% CR for 49 weeks. Although Ex and diet composition did not influence liver oncogenesis, CR prevented hepatic tumor formation. In addition, CR reduced steatosis, hepatocyte ballooning, inflammation, and immune cell infiltration, all of which are hallmarks in the progression of nonalcoholic fatty liver disease to liver tumorigenesis. RNA sequencing of nontransformed liver tissues from CR mice revealed changes in metabolic pathways and reduced inflammation, cytokine production, stellate cell activation and migration, and genes associated with liver injury and oncogenesis. These data demonstrate that CR protects against steatosis, liver inflammation, and liver injury and is a robust deterrent of carcinogen-induced hepatic oncogenesis. <i>Cancer Prev Res; 10(11); 660–70. ©2017 AACR</i>.</p></div>
<p>Fig. S1. Phenotypic and metabolic parameters are influenced by Ex and CR. Fig. S2. CR modulates additional markers of hepatic inflammation and immune cell infiltration. Fig. S3. CR causes divergence of genes in comparison to CTL mice. Fig. S4. CR affects gene signature pathways and networks associated with hepatic inflammation and metabolism. Table S1. Description of components (g/Kg) and macronutrient content (% kcal) of diets.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.