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Proceedings of the Society for Experimental Biology and Medicine 225:123-127 (2000)
© 2000 Society for Experimental Biology and Medicine

Original Article

Age-Related Changes in Rat Hepatic Acetyl-Coenzyme A Carboxylase

K. George Thampy, Michael J. Haas and Arshag D. Mooradian1,


Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri

Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in the synthesis 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-month-old male Fischer 344 rats. The mean (± SEM) activity of ACC (mU/mg protein) in liver homogenates from 4-month-old rats was 1.01 ± 0.14. There was an 80% increase in activity (1.83 ± 0.27) in 12-month-old rats (P < 0.01). However, there was significantly less activity (0.46 ± 0.06) in livers 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 avidin-affinity chromatography. The purified preparation migrated as a major protein band (Mr 262,000) on sodium dodecyl sulfate (SDS)-polyacrylamide gels. 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 Pi/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 significantly 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 specific activity and similar phosphate content; and (iii) the changes in ACC mRNA content of the liver paralleled the changes in total enzyme activity when 12-month-old rats were compared with 24-month-old rats whereas the increase in ACC activity in 12-month-old rats compared with 4-month-old rats could not be ascribed to changes in hepatic mRNA levels. These results indicate that the age-related changes in hepatic ACC occur at a post-translational level during early years of aging and at a pretranslational level at late states of senescence. These changes may contribute to the age-related alterations in body adiposity.






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