Peroxisomal beta-oxidation of fatty acids in neonatal swine

A high percentage of fatty acids in porcine milk but a limited capacity for hepatic mitochondrial $\beta$-oxidation in piglets, as well as their high rate of mortality, prompted a series of studies to examine development, importance, nutritional regulation, and inducibility of peroxisomal $\beta$-oxidation (POX) of fatty acids in piglets. POX activity in liver, kidney, and heart, measured either by an antimycin/rotenone-insensitive incubation method or by palmitoyl-CoA dependent KCN-insensitive reduction of NAD, developed rapidly during the postnatal period. Enzymatic assays confirmed a rapid postnatal development of fatty acyl-CoA oxidase (FAO) activity in piglet liver and kidney. The proportion of POX to total $\beta$-oxidation in these tissues was higher in pigs than in rats. Thus, POX in piglets may play an important role in oxidation of milk fatty acids. Hepatic POX activity in piglets was affected by nutritional state and is hypothesized to be regulated by the blood concentrations of free fatty acids or glucagon. A great increase of catalase activity during development was not in parallel with the development of FAO and resulted from both pre- and post-translational regulation. Evidence obtained by radio-HPLC analysis of media from incubations of (1-$\sp{14}$C) -palmitate with homogenates of the three tissues from newborn pigs revealed that acetate was one of the main end-products of both mitochondrial and peroxisomal $\beta$-oxidation. Thus, acetogenesis may be an important metabolic fate of acetyl-CoA generated from $\beta$-oxidation that is not coupled with ketogenesis or that is coupled to a limited ketogenesis. A substantial POX activity was present in the three tissues of piglets immediately after birth. POX was markedly induced in liver and heart, but not kidney or muscle, when neonatal pigs were fed milk replacer containing 0.5% clofibric acid. Total carnitine palmitoyltransferase activity in liver, heart, and kidney also was greatly induced. Aspirin (1.0%) only slightly induced hepatic POX. These results suggest that maternal administration of peroxisome proliferators might increase the capacities for peroxisomal and mitochondrial $\beta$-oxidation in newborn pigs, which in turn might increase the capacity to oxidize milk fatty acids and the capacity for thermogenesis.U of I OnlyETDs are only available to UIUC Users without author permissio