The influence of dietary fatty acids on the activity and metabolic control of peroxisomal carnitine palmitoyltransferase in the liver

Abstract

Peroxisomes play an important role in the β-oxidation of fatty acids and they possess a membrane-bound carnitine palmitoyltransferase (CPT). Whether this enzyme is regulated by the amount and type of fat consumed in the diet has not been investigated. Therefore weanling male Lewis rats were fed for various times (2 days to 4 weeks) on a low-fat (2.5% w/w) diet (LF) or on high-fat diets containing 20% (w/w) of either hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or menhaden (fish) oil (MO). Hepatic peroxisomal CPT activity and sensitivity to inhibition by malonyl CoA were examined. In general, feeding the high-fat diets resulted in higher CPT activity per mg peroxisomal protein (specific activity) and per g liver (capacity) than feeding the LF diet throughout the 4 week feeding period. The most rapid induction of CPT specific was seen in the livers of animals fed the SO, EPO and MO diets. Induction of CPT specific activity was maximal after one week of feeding each of the diets. Feeding the MO diet resulted in the highest CPT specific activity at most time points examined and the highest CPT capacity at all time points. In relation to feeding the LF diet, the HCO and EPO diets increased CPT specific activity and capacity by approximately 2-fold while the OO, SO and MO diets increased the CPT specific activity by 3- to 4-fold; these diets increased CPT capacity by 3.5-fold (OO), 4.5-fold (SO) and 7.4-fold (MO). These observations are consistent with previous observations that dietary fish oils increase peroxisomal β-oxidation. Peroxisomal CPT from animals fed the LF diet was the most sensitive to inhibition by malonyl CoA at each time point ([I 50] = approx. 0.5 μM). Each of the high-fat diets decreased the sensitivity of peroxisomal CPT to inhibition by malonyl CoA. The decrease in sensitivity was apparent after feeding the OO, SO or MO diets for 2 days. At all time points peroxisomal CPT from MO-fed rats was the least sensitive to malonyl CoA inhibition. At its least sensitive (after 7 days of feeding) peroxisomal CPT from MO-fed rats required a 5.7-fold higher malonyl CoA concentration to induce 50% inhibition than did the enzyme from LF-fed rats. These data indicate that both the level of fat in the diet and the fatty acid composition of high-fat diets influence CPT activity and its sensitivity to the inhibitor malonyl CoA.