Effect of neonatal hypoxia on the development of hepatic lipase in the rat
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Updated: Aug 3, 2026

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
1Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, USA. pclee@mcw.edu
Insights
Hypoxia increases plasma lipids in newborn rats by decreasing hepatic lipase activity, which delays lipid metabolism maturation. This effect is reversible after recovery from hypoxic conditions.
Area of Science:
- Biochemistry
- Physiology
- Developmental Biology
Background:
- Plasma lipid levels increase during hypoxia in suckling rats but not in weaned rats.
- Altered hepatic enzyme activity is a potential mechanism for hypoxia-induced hyperlipemia in neonates.
Purpose of the Study:
- To investigate the impact of hypoxia on hepatic lipid metabolism and enzyme activity in suckling and weaned rats.
- To determine the role of hepatic lipase in hypoxia-induced hyperlipemia during development.
Main Methods:
- Rats were exposed to 7 days of hypoxia from birth (suckling) or at 28 days of age (weaned).
- Hepatic lipid content, hepatic lipase activity, lactate dehydrogenase activity, transaminase activity, and CYP1A/CYP3A protein levels were measured.
- Recovery studies and dexamethasone administration were performed to assess reversibility and glucocorticoid effects.
Main Results:
- Hypoxia increased hepatic lipid content and decreased hepatic lipase activity in suckling rats only.
- Lactate dehydrogenase activity was reduced in hypoxic suckling rats; transaminase and CYP protein levels were unaffected.
- Hepatic lipase activity recovered to normal levels within 14 days after cessation of hypoxia.
- Dexamethasone administration mimicked the decrease in hepatic lipase observed in hypoxic neonates.
Conclusions:
- Hypoxia delays the normal maturation of hepatic lipase activity in newborn rats.
- Reduced hepatic lipase activity contributes to hyperlipemia in hypoxic suckling rats.
- The observed changes in hepatic lipase are developmentally regulated and reversible.
Abstract:
Increases in plasma lipids occur during hypoxia in suckling but not in weaned rats and may result from altered hepatic enzyme activity. We exposed rats to 7 days of hypoxia from birth to 7 days of age (suckling) or from 28 to 35 days of age (weaned at day 21). Hypoxia led to an increase in hepatic lipid content in the suckling rat only. Hepatic lipase was decreased to approximately 45% of control in 7-day-old rats exposed to hypoxia but not in hypoxic 35-day-old rats. Hypoxic suckling rats also had a 50% reduction in lactate dehydrogenase activity, whereas transaminase activity and CYP1A and CYP3A protein content were not different between hypoxic and normoxic groups. Additional rats were studied 7 and 14 days after recovery from hypoxic exposure from birth to 7 days of age; hepatic lipase activity had recovered to 85% by 7 days and to 100% by 14 days in the rats previously exposed to hypoxia. Administration of dexamethasone to neonatal rats to simulate the hyperglucocorticoid state found in hypoxic 7-day-old rats led to a moderate decrease ( approximately 75% of control) in hepatic lipases. Developmentally, in the normoxic state, hepatic lipases increased rapidly after birth and reached levels more than twofold that of the newborn by 7 days of age. Hypoxia delays the maturation of hepatic lipases. We suggest that the decrease in hepatic lipase activity contributes to hyperlipemia in the hypoxic newborn rats.

