Aspects of the hormonal regulation of hepatic carbohydrate and lipid metabolism
The liver is a major site in the rat for conversion of dietary carbohydrate into glycogen and triglyceride. Hepatic rates of fatty acid and glycogen synthesis were measured y vivo in response to meal-feeding (2h/day) by the incorporation of from 3H20. This technique has not been applied previously to glycogen synthesis and was validated in control and streptozotocin diabetic rats* Hepatic glycogen recycling was low in fed adult rats but was apparently greater in foetal rats. The precursor source for glycogen synthesis in vivo could not be determined from the distribution pattern of 3H incorporation. Hepatic glycogen synthesis was elevated in control rats for 5h after feeding. During this phase, glycogen could not have been a net precursor for other synthetic pathways® Hepatic fatty acid synthesis in control rats increased 20-fold 2h after feeding. This response was impaired and delayed, but not abolished, by streptozotocin diabetes (55mg/kg). Insulin pretreatment (30 P.Z.I.) restored the low diabetic rate of lipogenesis to normal by 8h after feeding. Streptozotocin reduced the hepatic Vmax activities of glucokinase, ATP-citrate lyase and total acetyl CoA carboxylase. None of these enzyme activities increased when hepatic fatty acid synthesis was stimulated by feeding in control rats or by feeding and insulin in diabetic rats. Feeding stimulated active acetyl CoA carboxylase in control, but not diabetic, rats. The regulation of hepatic fatty acid synthesis by both acetyl CoA carboxylase and increased substrate concentration is discussed. In control rats for the first 5h after feeding, hepatic glycogen could not have been a net fatty acid precursor. Thus the inhibition of hepatic fatty acid synthesis in this period by glucagon (Img/kg) could not have been directly due to depletion of glycogen® The glucagon inhibition of lipogenesis was abolished by adrenalectomy but not potentiated by corticotropin-treatment, suggesting a permissive role for glucocorticoid hormones. Adrenalectomy also impaired the inhibition of hepatic pyruvate kinase by glucagon but did not abolish the inactivation of pyruvate kinase by 10 )jM-cyclic AMP in vitro« The involvement of L-type pyruvate kinase in the regulation of hepatic fatty acid synthesis is discussed. The integrated regulation of the hepatic pathways of lipogenesis, glycolysis, gluconeogenesis and ketogenesis is considered.