Age-related changes in rat hepatic acetyl-coenzyme A carboxylase.
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 (M(r) 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 P(i)/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.
Thampy
K G
KG
Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri 63110, USA.
Haas
M J
MJ
Mooradian
A D
AD
D000103:Acetyl-CoA Carboxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000033:anatomy & histology; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D001483:Base Sequence; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D016375:Antisense Elements (Genetics); D008055:Lipids; D012333:RNA, Messenger; D000103:Acetyl-CoA Carboxylase