In contrast to the HFr-diet, neither the HFD- nor the NASH-diet resulted in increased plasma TG, even though high-fat diets have previously been shown to induce hypertriglyceridemia in rats . However, our findings agree with a recent study in mice investigating the contribution of dietary fat and cholesterol to NAFLD-development, which showed no effect of dietary fat and cholesterol on circulating TG or FFA levels, independently of whether these macronutrients were fed separately or in combination . One explanation could be that accelerated fat accumulation in the liver imposes a significant strain on metabolic pathways responsible for the release of lipids from the liver into plasma. Accordingly, it has been shown both in vitro and in vivo that high levels of fat and cholesterol in the liver result in increased stress in the endoplasmic reticulum, limiting secretion of apolipoprotein B100 (an essential component in the assembly of VLDL-particles) and thereby inhibits hepatic export of TG [29, 43]. The inflammatory profile was clearly distinguishable between groups in the present study. Systemic inflammation was present only in NASH-fed rats with higher circulating levels of haptoglobin. We also found increased levels of the pro-inflammatory cytokines MCP-1 and TNF-alpha in liver tissue homogenates in NASH-, HFD- and HFr- and in HFD-fed rats, respectively, suggesting progression of hepatic steatosis towards NASH with the increased inability of the liver to cope with fat infiltration. The inflammatory infiltrates observed histologically in livers of HFr- and NASH-fed rats at week 16, were reflected only in significantly higher levels of hepatic MCP-1, not TNF-alpha. Compared to the other diet-groups, NASH-fed rats might be expected to have the highest levels of liver inflammatory cytokines, due to the higher macrophage count, increased liver enzymes, and the more severe liver pathology. However, hepatic macrophages are a remarkably heterogeneous population of immune cells, whose effector function depends on origin, underlying pathogenesis and disease stage, which can result in high diversity in inflammatory cytokines released and cell surface markers [44, 45]. This could explain why the NASH-fed group does not have the highest hepatic MCP-1 and TNF-alpha levels despite the higher macrophage count and the more severe liver pathology. Despite increased hepatic MCP-1 levels in all groups compared to Control, MCP-1 plasma levels were below detection limit.