1. Maternal Low-Protein Diet or Hypercholesterolemia Reduces Circulating Essential Amino Acids and Leads to Intrauterine Growth Restriction
- Author
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Kum Kum S. Bhasin, Lisa J. Martin, Atila van Nas, Aldons J. Lusis, Sherin U. Devaskar, and Richard C. Davis
- Subjects
Male ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Inbred Strains ,Intrauterine growth restriction ,Blood lipids ,Inbred C57BL ,Medical and Health Sciences ,Mice ,Essential ,0302 clinical medicine ,Pregnancy ,Receptors ,Amino Acids ,Essential amino acid ,reproductive and urinary physiology ,2. Zero hunger ,chemistry.chemical_classification ,0303 health sciences ,Glucose tolerance test ,Fetal Growth Retardation ,medicine.diagnostic_test ,Female ,Leucine ,medicine.medical_specialty ,Offspring ,Hypercholesterolemia ,Protein-Restricted ,Mice, Inbred Strains ,Biology ,LDL ,Endocrinology & Metabolism ,03 medical and health sciences ,Low-protein diet ,Valine ,Internal medicine ,Glucose Intolerance ,Internal Medicine ,medicine ,Diet, Protein-Restricted ,Animals ,030304 developmental biology ,Animal ,Glucose Tolerance Test ,medicine.disease ,Dietary Fats ,Diet ,Mice, Inbred C57BL ,Pregnancy Complications ,Disease Models, Animal ,Endocrinology ,Metabolism ,chemistry ,Receptors, LDL ,Disease Models ,Amino Acids, Essential ,030217 neurology & neurosurgery - 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.
- Published
- 2009