Zinc Metabolism in Genetically Obese (ob/ob) Mice

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Abstract
Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from those in lean controls. In the present studies the absorption, retention and tissue distribution of zinc and constitutive levels of zinc-metallothionein (Zn-MT) in selected tissues were compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When 5-, 10- and 22-wk-old mice were administered 1.2 µmol 65Zn by stomach tube, the apparent absorption of 65Zn by obese mice was 1.5, 2.2 and 3.9 times higher, respectively, than that in age-matched lean mice. Retention of orally administered 65Zn after 96 h was also substantially higher in obese mice than in lean mice. To assess the possible influences of hyperphagia and intestinal hypertrophy on the enhanced apparent absorption of 65Zn by obese mice, food intake by an additional group of obese mice was restricted to that of age-matched lean controls. When actual absorption of zinc was determined according to the method of Heth and Hoekstra, groups of ad libitum–fed obese, pair-fed obese and lean mice absorbed 38, 32 and 18% of administered 65Zn, respectively. In contrast, the rate of 65Zn excretion 2–6 d after oral or subcutaneous administration of the metal was similar for obese and lean mice. Unrestricted and pair-fed obese mice had significantly lower percentages of carcass 65Zn present in skin, muscle plus bone, spleen and testes and higher percentages present in liver, small intestine and adipose tissue than lean mice. Similar differences between lean and obese mice were observed when total levels of zinc in tissues were determined. Constitutive levels of Zn-MT were significantly higher in small intestine, but lower in kidney and liver, of obese mice given free access to food compared to lean mice. Restricting food intake of obese mice to the amount consumed by lean mice significantly elevated concentrations of hepatic Zn-MT. These results show that several characteristics of zinc metabolism are altered in genetically obese (ob/ob) mice and that these differences are not merely due to hyperphagia and intestinal hypertrophy.