The possibility that postprandial
hyperinsulinemia could play a role in the development of hepatic
lipid disturbances during
convalescence from
influenza B
infection was explored in the ferret as a possible model of the steatosis of
Reye's syndrome. Postprandial
hyperinsulinemia was produced by feeding young ferrets
glucose/water and a regular diet (
glucose-treated group), as reflected by the mean serum
insulin levels attained, which were 57 and 135 microU/ml during control and postinfluenza periods, respectively. By comparison, ferrets fed water and a regular diet (untreated group) had mean
insulin levels of 19 and 22 microU/ml, while postprandial
glucose levels were comparable in the two groups of animals for each period. In contrast to untreated animals, grossly visible fatty livers were found in
glucose-treated ferrets during
convalescence. The total
lipid content of these livers had doubled compared with preinfection samples and compared with livers of untreated ferrets. By electron microscopy hepatic mitochondria showed striking changes with diminution of matrix density and reduction in cristae surface area only in convalescent samples from
glucose-treated animals. Serum
free fatty acid (FFA) levels were considerably higher in the
glucose-treated animals during fasting before
influenza and also after feeding during
convalescence. Serum
triglyceride (TG) levels were also high during
convalescence in the
glucose-treated group. Adipose tissue
lipoprotein lipase activities were similar between groups, but
hormone-sensitive lipase activity was twelvefold higher in
glucose-treated ferrets before and after
influenza B. These findings indicate that for a given stimulus,
glucose-treated ferrets would mobilize more FFA than untreated ferrets. The total capacity for beta-oxidation of FA by the mitochondrial pathway was identical in all groups of animals. Total
carnitine palmitoyl
transferase (
CPT) activity was the same in both control groups, but was significantly diminished in
glucose-treated animals during
convalescence. As
CPT regulates the entry of FA into the mitochondrial matrix, its reduction in response to higher
insulin concentrations would limit the oxidation of FA and stimulate TG accumulation. Therefore, the accumulation of
lipid in the liver in this model is regarded to have been caused by the simultaneous occurrence of increased lipolysis and increased hepatic TG synthesis owing, in part, to diversion of activated FA by
CPT, which is reduced in activity due to the regulatory action of
insulin. These findings may have pathophysiologic relevance for the
lipid changes that occur in
Reye's syndrome and to
fatty liver formation in hyperinsulinemic states.