FLEXIBILITY OF ZONATION OF FATTY-ACID OXIDATION IN RAT-LIVER

Periportal and perivenous hepatocytes were isolated from rats subjecte d to different treatments that induce (starvation, cold exposure) or d epress (refeeding after starvation) hepatic fatty acid oxidation. Thes e experiments were designed to determine factors that may be involved in creating and maintaining the asymmetrical distribution of this meta bolic pathway in the acinus of the liver, The uneven distribution of m itochondrial [C-14]-glutaryl-CoA synthase activity in starved animals, and (iv) was not determined by zonal differences in any of the follow ing parameters: sensitivity of carnitine palmitoyltransferase I to mal onyl-CoA, intracellular concentration of malonyl-CoA, fatty acid synth esizing capacity, acetyl-CoA carboxylase activity, fatty acid synthase activity or relative content of the two hepatic acetyl-CoA carboxylas e isoforms, Unlike mitochondrial oxidation, peroxisomal [C-14]palmitat e oxidation was always zonated towards the perivenous zone of the live r irrespective of the physiological status of the animal. The data pre sented show that changes in the acinar distribution of mitochondrial l ong-chain fatty acid oxidation involve specific long-term mechanisms u nder different physiological conditions.palmitate oxidation within the acinus (i) was very flexible and changed markedly with the physiologi cal status of the animal (periportal/perivenous ratio: 1.5, 2.0, 1.0 a nd 0.4 for fed, starved, refed and cold-exposed animals respectively), (ii) coincided with a similar zonation of carnitine palmitoyltransfer ase I activity in fed as well as in cold-exposed animals, (iii) was pa ralleled by a comparable zonation of mitochondrial 3-hydroxy-3-methyl-