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

Abstract

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.

Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

“…Pertinent to this study was the previous finding that dexamethasone resulted in marked hyperinsulinemia without a change in plasma glucose, indicating a state of relative insulin resistance ( 12 ). We also previously demonstrated that both leptin and ghrelin were increased by dexamethasone, but that only leptin was increased by hypoxia ( 15 ).…”

“…We have previously used this model of hypoxia and/or dexamethasone to examine endocrine and metabolic function in neonatal rats ( 12,14,15 ). Pertinent to this study was the previous finding that dexamethasone resulted in marked hyperinsulinemia without a change in plasma glucose, indicating a state of relative insulin resistance ( 12 ).…”

“…We have also demonstrated that ghrelin, a hormone released by the GI tract that has a wide variety of endocrine and metabolic actions, is increased by dexamethasone therapy ( 15 ). The differential actions of leptin and ghrelin on food intake, insulin sensitivity, and metabolic function made it clear that these two factors per se could not account for the changes in growth hormone ( 7 ), IGF-I ( 8 ), body composition ( 7,8 ), weight gain ( 7,8 ), lipid profiles ( 12,14 ), and other parameters of metabolic function in our previous studies.…”

“…Briefly, hypoxia from birth induces a decrease in weight gain without a significant change in body composition ( 7,8 ) and a state of relative insulin resistance ( 7,9,10 ). Furthermore, we have recently demonstrated that a tapering regimen of the glucocorticoid dexamethasone, administered to mimic clinical practice ( 11 ), results in hyperinsulinemia with normoglycemia and decreased weight gain ( 12 ). There is also a significant interaction between dexamethasone, which is often used to treat neonatal cardiopulmonary disorders ( 13 ), and hypoxia with respect to many parameters of metabolic function ( 12,14,15 ).…”

Histoquímica e morfometria da placenta de ratas tratadas com dexametasona

“…Outras situações em que se costuma aplicar o uso da dexametasona são os casos de gestação com risco de prematuridade, com o intuito de acelerar o desenvolvimento de determinados tecidos e órgãos do feto (Souza et al 2001, Bruder et al 2006.…”