A Piagen atherogenic diet induces hypercholesterolemia in mice causing chronic hepatic inflammation and steatosis that can lead to steatohepatitis. Feeding mice an atherogenic diet for 3-weeks significantly increases serum levels of cholesterol, AST and ALT, and leads to lipid deposition in hepatocytes. In addition, it stimulates the release of proinflammatory cytokines and the infiltration of inflammatory cells within the liver. This model can be used to study the pathogenesis of hepatic steatosis, inflammation and to screen novel compounds for the treatment of related hepatic diseases.
Preclinical Drug Efficacy Studies
After an initial acclimation period baseline blood serum is collected and body weight measurements are recorded. Immediately following, animals are placed on either an atherogenic or an isocaloric control chow diet. Body weight measurements are taken once/week throughout the duration of the study. The administration of therapeutic compounds is performed according to the schedule set-forth in the study protocol. At study completion, animals are sacrificed and blood is drawn through terminal means and processed to serum for downstream applications.
General clinical observations, body weight, serum chemistries for ALT, AST, bile and cholesterol, H&E staining to assess liver tissue for lipid vacuoles, inflammation, and tissue damage, cytokine profiling in blood serum using ELISA and Luminex multiplex assays, immunohistochemistry for protein expression and cellular distribution, and