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Metabolic Consequences of Hypoxia from Birth and Dexamethasone Treatment in the Neonatal Rat: Comprehensive Hepatic Lipid and Fatty Acid Profiling

Endocrine Research Laboratory (E.D.B., H.R.), St. Luke’s Medical Center, Milwaukee, Wisconsin 53215; and Department of Pediatrics (P.C.L.), Department of Pharmacology and Toxicology (P.C.L.), and Department of Medicine (H.R.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Address all correspondence and requests for reprints to: Hershel Raff, Ph.D., Endocrinology, St. Luke’s Physician’s Office Building, 2801 West Kinnickinnic River Parkway, Suite 245, Milwaukee, Wisconsin 53215. E-mail: hraff{at}mcw.edu.

Neonatal hypoxia is a common condition resulting from pulmonary and/or cardiac dysfunction. Dexamethasone therapy is a common treatment for many causes of neonatal distress, including hypoxia. The present study examined the effects of dexamethasone treatment on both normoxic and hypoxic neonatal rats. We performed comprehensive hepatic fatty acid/lipid profiling and evaluated changes in pertinent plasma hormones and lipids and a functional hepatic correlate, i.e. hepatic lipase activity. Rats were exposed to hypoxia from birth to 7 d of age. A 4-d tapering dose regimen of dexamethasone was administered on: postnatal day (PD)3 (0.5 mg/kg), PD4 (0.25 mg/kg), PD5 (0.125 mg/kg), and PD6 (0.05 mg/kg). The most significant finding was that dexamethasone attenuated nearly all hypoxia-induced changes in hepatic lipid profiles. Hypoxia increased the concentration of hepatic triacylglyceride and free fatty acids and, more specifically, increased a number of fatty acid metabolites within these lipid classes. Administration of dexamethasone blocked these increases. Hypoxia alone increased the plasma concentration of cholesterol and triacylglyceride, had no effect on plasma glucose, and only tended to increase plasma insulin. Dexamethasone administration to hypoxic pups resulted in an additional increase in plasma lipid concentrations, an increase in insulin, and a decrease in plasma glucose. Hypoxia and dexamethasone treatment each decreased total hepatic lipase activity. Normoxic pups treated with dexamethasone displayed increased plasma lipids and insulin. The effects of dexamethasone on hepatic function in the hypoxic neonate are dramatic and have significant implications in the assessment and treatment of metabolic dysfunction in the newborn.

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