Maternal Low-Protein Diet or Hypercholesterolemia Reduces Circulating Essential Amino Acids and Leads to Intrauterine Growth Restriction
- Kum Kum S. Bhasin1,
- Atila van Nas2,
- Lisa J. Martin2,
- Richard C. Davis1,
- Sherin U. Devaskar3 and
- Aldons J. Lusis124
- 1Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
- 2Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California
- 3Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California
- 4Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, California
- Corresponding author: Aldons J. Lusis, jlusis{at}mednet.ucla.edu
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.
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on 10 December 2008.
K.K.S.B., A.v.N., and L.J.M. are joint first authors of this work.
K.K.S.B. is currently affiliated with Kaiser Permanente Hospital, Bellflower, California.
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- Accepted November 26, 2008.
- Received October 26, 2007.
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