5B). The plasma TG levels were not significantly different between the three groups, but serum cholesterol was significantly higher in HFHC mice (372.3 ± 21.9 mg/dL) compared with both HF mice (277.3 ± 50.5 mg/dL; P < 0.001) and chow-fed mice (127.5 ± 7.1 mg/dL; P < 0.001) (Fig. 5E). Plasma oxCoQ 9 levels in mice at 16 weeks were significantly higher in HFHC mice (0.06 ± 0.004 μg/mL)

compared with HF mice (0.03 ± 0.004 μg/mL) and chow-fed mice (0.02 ± 0.004 μg/mL; P < 0.0001) (Table 2 and Fig. 5D). The correlation Vemurafenib concentration of liver tissue collagen 1 mRNA relative expression and absolute plasma oxCoQ 9 levels had an R2 value of 0.51. Thus, the fructose-containing HFHC diet had the most hepatic ROS, hypercholesterolemia, and hepatic fibrosis. This was mirrored by the levels of plasma oxCoQ9, which differed significantly among all three

groups and correlated with the presence of fibrosis in this model. The rising rates Sirolimus molecular weight of NASH make addressing the underlying causes of this serious condition more pressing. Hepatic steatosis is common in obese patients, but only a subset of these patients develop NASH, emphasizing the contribution of genetic and potential environmental risk factors. Human NASH histopathology has been associated with steatosis, lobular and portal inflammation, hepatocyte ballooning, and fibrosis. Specifically, zone 3 predominant macrovesicular steatosis, ballooning, and perisinusoidal fibrosis is deemed consistent with adult or type 1 NASH. Type 2 or pediatric NASH histopathology has been reported to have panacinar or periportal (zone 1) steatosis, rare ballooning and portal tract expansion by chronic inflammation or fibrosis.37 Individuals who have NASH with fibrosis have progressive disease and greater morbidity and mortality including the potential for cirrhosis, liver failure, and liver transplantation.3 However, the specific biological determinants that lead to development of NASH with fibrosis are not

well-defined. Fructose consumption accounts for approximately 10.2% of all calories in our average diet in the United States.38 In comparison with other simple sugars such as glucose, use of fructose for hepatic metabolism is not restricted by the rate-limiting click here step of phosphofructokinase, thus avoiding the regulating action of insulin.39 Fructose intake is two- to three-fold higher in patients with NASH compared with body mass index–matched controls, and daily fructose ingestion has been associated with increased hepatic fibrosis.40, 41 These epidemiologic data prompted us to investigate the potential mechanistic role that fructose and other simple sugars may play in the development of NASH. The present study focused on the development of a dietary model of NASH. To this end, we compared HF mice with mice maintained on the same diet but also given ad libitum access to fructose in their drinking water (HFHC).