Nonalcoholic steatohepatitis (NASH) is characterized by excess lipid accumulation and inflammation inhepatocytes. In this study, to provide insight into the preventive effects of d-allose, a rare sugar, on the onset of NASH, we designed animal experiments using male STAM mice treated with streptozotocin and fed a high-fat diet (HFD). Experiments were initiated when the mice reached 5 weeks of age and lasted 3 weeks. After the 3-week protocol, mice fed the HFD containing d-allose exhibited significantly decreased serum alanine aminotransferase levels, hepatic lipid accumulation and inflammation, and improved nonalcoholic fatty liver disease activity score compared to mice fed HFD without d-allose ( p < 0.05). Further, hepatic mRNA expression of sterol regulatory element binding protein-1 (Srebp-1) and monocyte chemotactic protein-1 (Mcp-1) was lower in mice fed d-allose.These results suggested that d-allose prevented NASH by blocking hepatic lipid accumulation and progressive inflammation.Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, rare sugar, d-allose
IntroductionNonalcoholic fatty liver disease (NAFLD) is an increasingly common hepatic phenotype of metabolic syndrome not caused by chronic alcohol consumption and is characterized by lipid accumulation in hepatocytes (Williams et al., 2011). Nonalcoholic steatohepatitis (NASH), a type of NAFLD, is a significant risk factor for the development of cirrhosis and hepatocellular carcinoma (Feldstein et al., 2009;Cohen et al., 2011). The two-hit theory (Day and James, 1998) and multiple parallel hits hypothesis (Tilg et al., 2010) have been used to explain the progression of simple steatosis to NASH via lipid accumulation, inflammation, and oxidative stress in the liver, although the exact mechanisms R. Yamamoto et al. 320 have not yet been elucidated.In the alternative medicinal food sciences, recent reports have claimed that excessive sugar intake (e.g., d-fructose and highfructose corn syrup) is a high risk factor in the progression of NAFLD/NASH (Abdelmalek et al., 2010;Nseir et al., 2010).Meanwhile, the physiological effects of rare sugars, such as shown to protect against inflammatory and oxidative ischemia/ reperfusion (I/R) injury in liver, retinal, and cerebral injuries in rodent models (Hossain et al., 2003;Hirooka et al., 2006;Gao et al., 2013). Previous studies have revealed the physiological benefits
Materials and MethodsAnimals and experimental design, and sample preparation STAM mice were used to model NASH and were obtained according to the method described by Fujii et al. (2013). Pathogenfree, 14-day pregnant female C57BL/6J mice were purchased from Charles River Laboratories (Tokyo, Japan). To induce NASH, STAM mice were primarily obtained by treating C57BL/6J mice with a single subcutaneous injection of 200 µg STZ (SigmaAldrich, St. Louis, MO, USA) 2 days after birth. At 4 weeks of age, the mice were fed a HFD (HFD32; CLEA Japan, Tokyo, Japan) ad libitum for 1 week (the experimental scheme is shown in Fig. 1). At 5 ...