Rodent Plasmodium development in livers of genetically obese Zucker rats (fa/fa)

Factors involved in Plasmodium yoelii yoelii hepatic schizont development still remain partly puzzling, raising the question of the host cell contribution to parasite growth. Among others, the hepatocyte lipid content could play a key role as has been suggested in the natural host which presents spontaneous fatty liver features. Single gene mutated Zucker rats (fa/fa) develop a massive obesity characterized early in life by increased lipid content in the liver. We have studied the infection efficiency of the same sporozoite inoculum in fa/fa compared to lean (Fa/fa) rats. Injection of the same number of sporozoites resulted in a four times higher number of parasitized hepatocytes in fa/fa than in Fa/fa control rats. In addition, schizonts developing in fa/fa livers were bigger and gave rise to infectious merozoites inducing more severe parasitemia. These data indicate that the fatty genotype could account for permissive in situ conditions facilitating the parasite development. Comparing fa/fa with Fa/fa liver plasma membranes for fatty acid composition of the total phospholipids and fluorescence polarisation of a DPH probe, we measured (i) differences in fatty acid composition; more 16:1n-7, accumulation of both 20:5n-3 and 22:5n-3 (two precursors of 22:6n-3) and more 20:3n-6, (ii) a significant elevation of plasma membrane fluidity. Our results indicate that the fa/fa hepatocyte is a good model for studying parasite-host cell interactions in relation with lipid metabolism.