Covariance of tricarboxylate carrier activity and lipogenesis in liver of polyunsaturated fatty acid (n-6) fed rats

The mitochondrial tricarboxylate (citrate) carrier plays an important role in hepatic intermediary metabolism because, among other functions, it suppl ies the cytosol with acetyl units for fatty-acid synthesis. In this study, the effect of polyunsaturated fatty acids (PUFA, n-6) on the function of th is mitochondrial transporter and on lipogenic enzyme activities was investi gated by feeding rats for 4 weeks with a 15%-fat diet composed of high lino leic safflower oil. Citrate transport was strongly reduced in liver mitocho ndria isolated from PUFA-treated rats. A reduced transport activity was als o observed when solubilized mitochondrial citrate carrier from PUFA-treated rats was reconstituted into liposomes. In the same animals, a decrease of cytosolic lipogenic enzyme activities was observed. These results indicate a coordinated modulation of citrate carrier and of lipogenic enzyme activit ies by PUFA feeding. Kinetic analysis of the carrier activity showed that o nly V-max decreased, whereas K-m was almost virtually unaffected. The PUFA- mediated effect is most likely due to the reduced mRNA level and lower cont ent of the citrate carrier protein observed in the safflower oil-fed rats.