Abstract
Dietary arginine (Arg) supplementation has been proposed to have positive effects on the development of liver diseases. In the present study, we investigate if an oral Arg supplementation in diet protects mice fed a fructose, fat and cholesterol enriched Western-style diet (WSD) from the development of non-alcoholic steatohepatitis (NASH). Female C57BL/6J mice were fed a liquid control diet or a liquid WSD ± Arg (2.49 g/kg body weight/day) for 6 weeks. Indices of liver injury, glucose metabolism and intestinal permeability were determined. While Arg supplementation had no effects on body weight gain, fasting blood glucose levels were significantly lower in WSD+Arg-fed mice than in C+Arg-fed animals. WSD-fed mice developed liver steatosis accompanied with inflammation, both being significantly attenuated in WSD+Arg-fed mice. These effects of Arg supplementation went along with a protection against WSD-induced decreased tight junction protein levels in the upper parts of the small intestine, increased levels of bacterial endotoxin in portal plasma as well as increased hepatic toll-like receptor-4 mRNA and 4-hydroxynonenal protein adduct levels. In conclusion, Arg supplementation may protect mice from the development of NASH.
Highlights
Materials and methodsBesides the metabolic syndrome, conditions like obesity, type 2 diabetes and dyslipidemia are strongly associated with non-alcoholic fatty liver disease (NAFLD), which is increasingly becoming a worldwide health problem
TNFα protein levels were significantly higher in livers of Western-style diet (WSD)-fed mice when compared to their respective control group, while protein levels of TNFα did not differ between groups fed diets supplemented with Arg
Alterations of intestinal microbiota composition and barrier function resulting in an increased permeation of bacterial endotoxin into the portal blood have repeatedly been shown to be associated with the development of NAFLD
Summary
Materials and methodsBesides the metabolic syndrome, conditions like obesity, type 2 diabetes and dyslipidemia are strongly associated with non-alcoholic fatty liver disease (NAFLD), which is increasingly becoming a worldwide health problem (for overview see Zhang and Lu 2015). Results of human and animal studies suggest that dietary pattern and alterations in the intestine like changes in microbiota and barrier function, may contribute to the development of the disease (Boursier et al 2016; Tilg and Moschen 2010; Volynets et al 2012). Oral Arg supplementation has been shown to attenuate lipopolysaccharide-induced inflammatory response (Tan et al 2014) and to decrease bacterial translocation in the intestine in animal models (Quirino et al 2013). We hypothesized that via its role in inflammatory process and gut functions, Arg supplementation may limit the progression of early stages of NAFLD to NASH. The present study aimed to investigate if an oral Arg supplementation protects mice from the onset of a Western-style diet (WSD)-induced NASH and if so, to delineate responsible molecular mechanisms
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