Pathogenesis of fatty liver in rats fed a high protein diet without pyridoxine

Fatty liver induced in rats by a high protein diet without pyridoxine was studied morphologically. The microscopic change was characterized by accumulation of fat in hepatocytes of the centrolobular and midzonal areas. Electron microscopic examination at an early stage showed marked accumulation of small osmiophilic particles in the granular endoplasmic reticulum and vesicles throughout the cytoplasm with similar particles in the spaces of Disse. After 4 weeks, numerous lipid droplets of various sizes were seen in pericanalicular lysosomes in hepatocytes with concomitant increase in the triglyceride level. The droplets gradually formed larger droplets in the cytoplasm. After 8 weeks, myelin figures together with fat droplets were seen in continuity with the endoplasmic reticulum and occasionally crystal clefts were observed within lysosomes of hepatocytes. These findings suggest that development of fatty liver results from impaired lysosomal degradation of lipid.