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Zinc Metabolism in Genetically Obese (ob/ob) Mice^1,2,

Martha L. Kennedy^*,3 and Mark L. Failla^,4

^* Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705

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.

KEY WORDS: • zinc • zinc-65 • zinc absorption • zinc excretion • metallothionein • obesity • ob/ob mice

¹ Supported by USDA Competitive Research Grants Program (Grant No. 85-CRCR-1-1610) and the John L. Pratt Animal Nutrition Program at Virginia Polytechnic Institute and State University.

² A preliminary report of this work was presented at the 1986 Annual Meeting of the Federation of American Societies for Experimental Biology, St. Louis, MO, April 13–18. Kennedy, M. L. & Failla, M. L. (1986) Zinc metabolism in genetically obese mice. Fed. Proc. 45: 1086 (abs.).

³ Current address: Department of Nutrition, University of California, Davis, CA 95616.

⁴ To whom correspondence should be addressed.

Manuscript received 2 July 1986. Revision accepted 16 January 1987.

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