Pathophysiologic Aspects of Feline Hepatic Lipidosis

Abstract

Feline hepatic lipidosis (FHL) is considered the most common hepatobiliary disease in cats. It is characterized by the excessive accumulation of fat, in the form of triglycerides, in more than 80% of the hepatocytes resulting in secondary impairment of liver function, and intrahepatic cholestasis. Feline hepatic lipidosis presents as an acute critical syndrome that can result in the animal’s death due to severe liver dysfunction and failure if therapeutic measures are not taken expeditiously. The pathophysiologic mechanisms leading to the accumulation of fat in hepatocytes and FHL are not yet completely understood. Most likely, they consist of disturbances in the pathways that regulate uptake, synthesis, degradation, and secretion of fatty acids. The aim of this thesis is to unravel the characteristics of the different pathways of lipid mobilisation, hepatic lipid metabolism and de novo lipid synthesis in healthy cats and cats with FHL. The effect of sex hormones on the lipid metabolism of healthy cats, and the lipid profile and the activation of progenitor cells in cats affected with hepatic lipidosis have been evaluated. Considering the results from our studies and data derived from experimental studies of overweight cats undergoing rapid weight loss and induction of hepatic lipidosis, we can argue that both limitations in lipid mobilisation from the liver and increased de novo hepatic lipid synthesis are unlikely to be important causes of hepatic lipid accumulation in FHL. The most likely pathophysiologic pathway appears an insufficient increase in the rate of fatty-acid oxidation in the face of increased peripheral lipid mobilization.