Type of Steatosis Influences Microcirculation and Fibrogenesis in Different Rat Strains

Abstract

ABSTRACTThis study investigates the impact of rat strain on the development of nonalcoholic fatty liver disease (NAFLD) focusing on morphological features and microcirculation. Male rats of Lewis, Wistar, and Sprague Dawley (n = 6 per strain and group) were randomized into a high-fat group which was fed with a special high-fat nutrition for a 3-week period and a control group which received standard nutrition. Intravital microscopy was used for the evaluation of microcirculation and correlated to morphological changes using a fatty liver scoring system. All three strains receiving a high-fat diet developed a grade 3 steatosis (>66% liver cell steatosis). Whereas Lewis showed a solely microvesicular steatosis, Wistar developed a mixed form and Sprague Dawley showed a pure macrovesicular steatosis and the highest degree of fibrosis and hepatocyte damage. Microcirculatory results revealed that sinusoidal density was already affected by a microvesicular steatosis and decreased with increasing macrovesicular proportion (Lewis: 18%, Wistar: 31%, Sprague Dawley: 23%). The degree of steatosis correlates with reduced blood flow velocity in central veins as well as in sinusoids (Lewis: 28%, Wistar: 39%, Sprague Dawley 44%). The densities of hepatocytes and hepatic stellate cells were only impaired once macrovesicular cell steatosis (Wistar and Sprague Dawley) was present. The development of NAFLD in the rat revealed strain-specific morphological features correlating with microcirculatory changes that should be considered in further studies using these models.