Hormonal regulation of acetyl-CoA carboxylase in epididymal adipose tissue

Treatment of rat epididymal adipose tissue with insulin for a few minutes leads to a substantial increase in the rate of fatty acid synthesis, which is explained in part by rapid activation of the cytoplasmic enzyme acetyl-CoA carboxylase (Denton, 1975; Denton et al., 1977; Brownsey & Denton, 1979). The effects of insulin on fatty acid synthesis are opposed by adrenaline, but the changes in kinetic properties of acetyl-CoA carboxylase brought about by the two hormones are complex and appear to indicate discrete actions of the two hormones on the enzyme (Brownsey et al., 1981~) . Such short-term effects, probably reflecting changes in the proportion of the enzyme in its active polymeric form, persist into tissue extracts with high dilution after treatment of tissue with hormones either in vitro (Lee et al., 1973; Halestrap & Denton, 1973, 1974) or in vivo (Stansbie et al., 1976; McCormack & Denton, 1977), and are distinct from long-term events involving changes in rates of protein synthesis or degradation (fully discussed by Volpe & Vagelos, 1976; Lane et al., 1974; Numa & Yamashita, 1974). The aim of the present communication is to describe experiments performed in this laboratory that indicate that the different effects of insulin and adrenaline on the activity of acetyl-CoA carboxylase are unlikely to be explained by changes in concentrations of the allosteric effectors citrate and fatty acyl-CoA esters, but rather are probably to be explained by increased phosphorylation of different specific sites on the enzyme.