Age-related changes in rat hepatic acetyl-coenzyme A carboxylase

Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in the synthe sis of long-chain fatty acids. Since aging influences adiposity, we studied the activity of ACC and its mRNA content in livers of 4-, 12-, and 24-mont h-old male Fischer 344 rats. The mean (+/- SEM) activity of ACC (mU/mg prot ein) in liver homogenates from 4-month-old rats was 1.01 +/- 0.14. There wa s an 80% increase in activity (1.83 +/- 0.27) in 12-month-old rats (P < 0.0 1). However, there was significantly less activity (0.46 +/- 0.06) in liver s of 24-month-old rats (P < 0.001). The total activity of ACC (per g liver) followed the same trend. The enzyme from all age groups was purified by av idin-affinity chromatography, The purified preparation migrated as a major protein band (M-r 262,000) on sodium dodecyl sulfate (SDS)-polyacrylamide g els. The specific activity of the purified preparation was 1.5, 1,8, and 1. 8 U/mg for 4-, 12-, and 24-month-old rats, respectively. The alkali-labile phosphate content was 5.66 +/- 0.17, 5.64 +/- 0.21,and 6.21 +/- 0.35 mols P -l/mole subunit for 4-, 12-, and 24-month-old rats, respectively. These age -related differences were not significant. The hepatic ACC mRNA measured by ribonuclease protection assay when corrected for G3PDH mRNA was significan tly reduced in 24-month-old rats (0.24 +/- 0.03) compared with 12-month-old (0.58 +/- 0.04) or 4-month-old rats (0.43 +/- 0.007) P< 0.01, In summary: (i) Aging in rats is associated with significant changes in ACC activity; ( ii) the purified ACC preparations from the three age groups had similar spe cific activity and similar phosphate content; and (iii) the changes in ACC mRNA content of the liver paralleled the changes in total enzyme activity w hen 12-month-old rats were compared with 24-month-old rats whereas the incr ease in ACC activity in 12-month-old rats compared with 4-month-old rats co uld not be ascribed to changes in hepatic mRNA levels. These results indica te that the age-related changes in hepatic ACC occur at a post-translationa l level during early years of aging and at a pretranslational level at late states of senescence. These changes may contribute to the age-related alte rations in body adiposity.