Dehydroepiandrosterone, a mammalian glucose-6-phosphate dehydrogenase inhibitor, prevented Avy/a mice from becoming obese. Decreased accumulation of triacylglycerol accounted for a large portion of the weight difference between treated and control Avy/a mice. Hepatic lipogenesis as measured by 3H2O incorporation into total lipid was less in the dehydroepiandrosterone-treated mice. Dehydroepiandrosterone did not suppress appetite and had no apparent toxic effects at the doses used, and its weight controlling effects were reversible upon withdrawal of treatment.
Genetically obese, diabetic and hypercholesterolemic C57BL/6J-ob/ob mice were placed on Purina Laboratory Chow containing 2% cholesterol for up to 4 months. They developed higher plasma cholesterol levels and accumulated an increased quantity of cholesterol in the liver but failed to develop atherosclerotic lesions in the aorta as would be expected in an obese, diabetic and hypercholesterolemic human adult.
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