THE EFFECT OF DIETARY-LIPID MANIPULATION ON HEPATIC MITOCHONDRIAL PHOSPHOLIPID FATTY-ACID COMPOSITION AND CARNITINE PALMITOYLTRANSFERASE-I ACTIVITY

The maximal activity of the overt form of carnitine palmitoyltransfera se I (CPT I; EC 2.3.1.21) and its sensitivity to inhibition by malonyl CoA were measured in mitochondria prepared from the livers of rats wh ich had been fed for 10 weeks on either a low fat diet (LF; 2.4% fat b y weight) or on one of four high fat diets which contained 20% by weig ht of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO) or menhaden (fish) oil (MO). CPT I activity (i.e. activity p er g of liver tissue), was elevated in animals fed the the OO, SO or M O diets compared with those fed the LF or HCO diets. Feeding the HCO d iet did not result in elevation of CPT I activity compared with feedin g the LF diet. CPT I specific activity (i.e. activity per mg mitochond rial protein) was elevated in animals fed SO diet, but not in animals fed any of the other high fat diets. These observations suggest that a n elevated fat load is not solely responsible for increasing CPT I act ivity, but that the fatty acid composition of the diet also plays a ro le. Hepatic CPT I activity of rats fed the LF diet was most sensitive to inhibition by malonyl CoA ([I-50]= 0.53 mu M). Each of the high fat diets decreased the sensitivity of CPT I to inhibition by malonyl CoA ; CPT I activity in the livers from animals fed the MO diet was the le ast sensitive to malonyl CoA inhibition ([1(50)]= 1.8 mu M). The fatty acid compositions of the major mitochondrial membrane phospholipids, phosphatidylcholine, phosphatidylethanolamine and cardiolipin were mod ified according to the fatty acid composition of the diet. Each of the se phospholipids had a distinct fatty acid composition and similar eff ects of dietary lipid manipulation on the fatty acid compositions were observed. Feeding the SO diet resulted in fatty acid compositions whi ch were most similar to those found after feeding the LF diet. Feeding the HCO and OO diets increased the proportions of stearic and oleic a cids, respectively, while decreasing the proportion of linoleic acid. Feeding the MO diet resulted in increased proportions of palmitic, pal mitoleic, eicosapentaenoic and docosahexaenoic acids and decreased pro portions of linoleic and arachidonic acids in each of the phospholipid s. It is proposed that the effects of dietary lipid manipulation upon CPT I activity and sensitivity to inhibition by malonyl CoA are due to alterations in the fatty acid composition of the phospholipids in the mitochondrial membrane where CPT I resides.