Maternal Low-Protein Diet or Hypercholesterolemia Reduces Circulating Essential Amino Acids and Leads to Intrauterine Growth Restriction

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 front two mouse models for IUGR: 1) feeding C57BL/6J darns a protein-restricted diet and 2) feeding C57BL/6J LDL receptor-null (LDLR-/-) darns 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. Tire 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 titters 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. Diabetes 58:559-566, 2009