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Perinatal development of hepatic cholesterol synthesis in the rat
Insights
Perinatal rat liver cholesterol synthesis rates and HMG CoA reductase activity were studied. Despite high reductase activity, cholesterol synthesis declined before birth, suggesting other regulatory factors are involved.
Area of Science:
- Biochemistry
- Developmental Biology
- Lipid Metabolism
Background:
- Cholesterol synthesis and HMG CoA reductase activity in rat liver are known to be high before birth and low after birth.
- The precise timing of the decline in perinatal cholesterol synthesis rates remains uncertain.
Purpose of the Study:
- To determine in vivo rates of cholesterol synthesis and hepatic reductase activity in perinatal rats.
- To analyze plasma, liver, and microsomal lipid composition during the perinatal period.
Main Methods:
- In vivo cholesterol synthesis rates were measured using [3H]water.
- Hepatic reductase activity was assessed in vitro.
- Lipid composition of plasma, liver, and microsomes was determined.
Main Results:
- HMG CoA reductase activity increased during late gestation, peaked after birth, and declined with suckling.
- In vivo cholesterol synthesis increased from gestation day 18-20 but decreased the day before birth.
- Plasma and liver cholesterol and triacylglycerol levels increased significantly within 48 hours after birth.
Conclusions:
- The low in vivo rate of hepatic cholesterol synthesis in late gestation and before suckling may not be solely due to low HMG CoA reductase activity.
- Changes in microsomal cholesterol/phospholipid ratio and fatty acid unsaturation index suggest complex lipid regulation during this period.
Abstract:
Rates of cholesterol synthesis and HMG CoA reductase activity in rat liver, have been reported to be high before and low after birth. The timing of the decline in perinatal rates of cholesterol synthesis, however, is uncertain. These studies, therefore, determined in vivo rates of cholesterol synthesis using [3H]water and hepatic reductase activity in vitro in perinatal rats. The lipid composition of the plasma, liver and its microsomal subfraction were also determined. Reductase activity increased during late gestation, remained high immediately after birth, then decreased with the commencement of suckling. Rates of cholesterol synthesis increased from gestation day 18 to 20, but in contrast to reductase activity, decreased on the day before birth. Plasma cholesterol and triacylglycerol levels increased to gestation day 19, then decreased to term. By the 6th h after birth, plasma and liver cholesterol and triacylglycerol levels had increased markedly. By 48 h after birth, the high hepatic cholesterol content was associated with an increase in the cholesteryl ester fraction. The microsomal cholesterol/phospholipid molar ratio decreased from gestation day 16 until 12 h after birth, then increased markedly from 36 to 48 h. There was an apparent inverse relationship between the change in microsomal cholesterol/phospholipid molar ratio and the fatty acid unsaturation index from gestation day 16 to 36 h after birth. The results suggest that in late gestation and before suckling, the low in vivo rate of hepatic cholesterol synthesis may not be due to low activity of HMG CoA reductase.