ABSTRACT
OBJECTIVE: We have examined maternal mechanisms for adult-onset glucose intolerance, increased adiposity, and atherosclerosis using two mouse models for intrauterine growth restriction (IUGR): maternal protein restriction and hypercholesterolemia. RESEARCH DESIGN AND METHODS: For these studies, we measured the amino acid levels in dams from two mouse models for IUGR: 1) feeding C57BL/6J dams a protein-restricted diet and 2) feeding C57BL/6J LDL receptor-null (LDLR(-/-)) dams a high-fat (Western) diet. RESULTS: Both protein-restricted and hypercholesterolemic dams exhibited significantly decreased concentrations of the essential amino acid phenylalanine and the essential branched chain amino acids leucine, isoleucine, and valine. The protein-restricted diet for pregnant dams resulted in litters with significant IUGR. Protein-restricted male offspring exhibited catch-up growth by 8 weeks of age and developed increased adiposity and glucose intolerance by 32 weeks of age. LDLR(-/-) pregnant dams on a Western diet also had litters with significant IUGR. Male and female LDLR(-/-) Western-diet offspring developed significantly larger atherosclerotic lesions by 90 days compared with chow-diet offspring. CONCLUSIONS: In two mouse models of IUGR, we found reduced concentrations of essential amino acids in the experimental dams. This indicated that shared mechanisms may underlie the phenotypic effects of maternal hypercholesterolemia and maternal protein restriction on the offspring.
Subject(s)
Amino Acids, Essential/blood , Diet, Protein-Restricted/adverse effects , Dietary Fats/adverse effects , Fetal Growth Retardation/etiology , Hypercholesterolemia/blood , Pregnancy Complications/blood , Amino Acids/blood , Amino Acids, Essential/deficiency , Animals , Disease Models, Animal , Female , Glucose Intolerance/epidemiology , Glucose Tolerance Test , Hypercholesterolemia/complications , Male , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Pregnancy , Receptors, LDL/deficiency , Receptors, LDL/geneticsABSTRACT
In vitro studies have suggested that a fraction of human high density lipoprotein (HDL), termed trypanosome lysis factor (TLF), can protect against trypanosome infection. We examined the involvement of two proteins located in the TLF fraction, apolipoprotein A-II (apoA-II) and paraoxonase 1 (PON1), against trypanosome infection. To test whether PON1 is involved in trypanosome resistance, we infected human PON1 transgenic mice, PON1 knockout mice, and wild-type mice with Trypanosoma congolense. When challenged with the same dosage of trypanosomes, mice overexpressing PON1 lived significantly longer than wild-type mice, and mice deficient in PON1 lived significantly shorter. In contrast, mice overexpressing another HDL associated protein, apoA-II, had the same survival as wild-type mice. Together, these data suggest that PON1 provides protection against trypanosome infection. In vitro studies using T. brucei brucei indicated that HDL particles containing PON1 and those depleted of PON1 did not differ in their lysis ability, suggesting that protection by PON1 is indirect. Our data are consistent with an in vivo role of HDL protection against trypanosome infection.
