Lipid metabolism appears to be less zonated than carbohydrate and protein
metabolism. Studies on the zonation of lipid metabolism have been centered in particular on
fatty acid synthesis which, according to the concept of metabolic zonation, should be a
predominantly perivenous process while fatty acid oxidation should be periportal. There are,
however, conflicting data on the activity gradients of lipogenic enzymes as well as measurements
of actual synthesis of fatty acid and very low density lipoprotein. Data obtained by
microdissection show a 1.5- to 2-fold higher activity of acetyl-CoA carboxylase and citrate
lyase in the perivenous zone in agreement with measurements of the actual rate of fatty acid
synthesis in preparations of hepatocyte, enriched in periportal or perivenous cells. On the
other hand, results obtained with the dual-digitonin-pulse perfusion technique demonstrate
the opposite gradient in the form of a 2- to 3-fold higher specific activity of acetyl-CoA
carboxylase in the periportal zone based on measurements of the acetyl-CoA carboxylase
protein proper. This specific activity gradient, which applies to male and not female rats,
disappears almost completely in the fasted-refed animal, were lipogenesis is strongly
induced. In this review we attempt to rationalize these discrepancies in the results as methodological
differences which in particular apply to the following parameters: (1) expression
of results (reference substance); (2) selectivity of zonal sampling, and (3) differences in
methodology of acetyl-CoA carboxylase measurements. It is concluded that these factors
could account for the discrepancies, but further studies, in particular on the zonation acetyl-
CoA carboxylase mRNA, are required in order to further understand the zonation of lipid
metabolism and its possible role in the metabolic regulation of the liver.