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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:1028-1031, May 2004


Biochemical and Molecular Actions of Nutrients
Research Communication

Dietary Phytoestrogens Increase Metabolic Resistance (Cold Tolerance) in Long-Chain Acyl-CoA Dehydrogenase–Deficient Mice1

A. Michele Schuler*, Stephen Barnes{dagger}, Barbara A. Gower** and Philip A. Wood*,**,2

Departments of * Genetics, {dagger} Pharmacology and Toxicology, and ** Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL

2To whom correspondence should be addressed. E-mail: paw{at}uab.edu.

We evaluated the role of dietary phytoestrogens (PE) in the disease phenotype of cold intolerance that characterizes long-chain acyl-CoA dehydrogenase–deficient (LCAD–/–) mice, a model of inborn errors of mitochondrial fatty acid ß-oxidation. Male LCAD–/– mice were fed a standard diet containing endogenous PE, a PE-free diet, or a PE-free diet that was supplemented with genistein (250 µg/g diet). The standard diet did not restore complete cold tolerance, but it provided more resistance (P = 0.004) to cold challenge than the PE-free diet. There was a nonsignificant difference (P < 0.07) between LCAD–/– mice fed the genistein-supplemented diet and those fed the PE-free diet. There were no differences in end-point serum glucose concentrations among the 3 groups. Serum FFA were decreased in LCAD–/– mice fed the standard diet compared with those fed the PE-free diet (P = 0.005) and the diet supplemented with genistein (P < 0.001). Serum triglyceride concentrations were greater (P < 0.05) only in LCAD–/– mice fed the genistein-supplemented diet than those fed the standard diet. These results demonstrate the beneficial effects of dietary PE on metabolic tolerance in LCAD–/– mice. Furthermore, they suggest changes that could improve pediatric formula constituents, especially with regard to management of children with inborn errors of fatty acid oxidation.


KEY WORDS: • phytoestrogens • genistein • long-chain acyl-CoA dehydrogenase • cold tolerance







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