The role of insulin in the control of hepatic fatty acid and glycerolipid metabolism assessed by studies in vivo.

The liver secretes triacylglycerol-rich very-low-density lipoproteins (VLDL). Teleologically, it would be expected that during the prandial/early absorptive period the rate of hepatic VLDL secretion would be inhibited, in view of the concomitant secretion of chylomicrons from the gut. Such inhibition would limit the extent and duration of post-prandial hyperlipaemia. Experiments in which the fatty acids of the liver were labelled specifically in rats in vivo show that, during a mean, triacylglycerol secretion was inhibited through a combination of diversion of flux towards phospholipid synthesis, and inhibition of the fractional rate of secretion of triacylglycerol. These adaptations occur even in diabetic rats, indicating that insulin is not obligatorily involved in mediating them. It is suggested that uptake of osmolytes (e.g. amino acids that are cotransported with Na+ ions into hepatocytes) from the portal circulation may result in increased hepatocyte volume and that this, in turn, alters fatty acid and glycerolipid metabolism independently of, but possibly in synergy with, insulin action.