Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning

We examined whether the Fas (APO-1/CD95)/Fas ligand system mediates apoptos is in rats with ventromedial hypothalamus (VMH) lesions. Northern and Weste rn blotting indicated that VMH lesions lead to a significant increase in Fa s mRNA and protein expression from day 1 to day 7 and in Fas ligand mRNA an d protein expression from day 2 to day 7. Immunohistochemistry indicated th at the region of strongest Fas expression shifted from acinar zone 1 to zon es 2 and 3 by day 7 after VMH lesioning and that at days 2-7 Fas-ligand-pos itive hepatocyte cell membranes and cytoplasm were randomly distributed in acinar zones 1-3. We also analyzed activation of caspase 3-like proteases i n hepatocytes, Kupffer cells, and sinusoidal endothelial cells. Spectrofluo rometric assay demonstrated that caspase 3-like activity significantly incr eased only in hepatocytes after VMH lesioning. Moreover, electron microscop y and TUNEL assay showed that VMH lesions induced apoptosis. All of these e ffects were completely inhibited by hepatic vagotomy and administration of atropine. Vagal firing after VMH lesioning may stimulate Fas/Fas ligand sys tem-mediated apoptosis through the cholinergic system in the rat liver.