Adipophilin, Fatty Liver Disease

Fatty liver disease (FLD) is a disease that is normally associated with alcoholism or obesity in humans. This reversible condition is an abnormal retention of fat within the hepatocytes and results in an accumulation of large triglyceride fat vacuoles in the liver. Defects of the fat metabolism are responsible for the pathogenesis of fatty liver. Therefore, metabolic diseases that affect the normal metabolism of fat can also cause fatty liver disease. At the early stages, the fatty changes will be microvesicular, meaning that multiple fat droplets will fill the liver cells, without dislodging the nucleus. In later stages the changes become macrovesicular as the nucleus is forced to the periphery of the vacuole. These vacuoles are represented as sharply demarcated empty spherical spaces within the cytoplasm of hepatocytes. The fatty change becomes irreversible when the vacuoles combine and form fatty cyst lesions.

Quantification of fat vacuoles in a fatty liver is relevant in many applications. In toxicological pathology, the two main areas of interest are common toxicological change and prognosis of alcoholic liver disease. In drug development, a fatty liver will be an indicator of a toxic effect on metabolism in toxicology screenings. By extracting information about both number and area distribution of the fat vacuoles, the toxic effect of the drug (or efficacy if it is a treatment study) can be quantified and the stage of the fatty liver disease can be determined.