Thyroid Function of Genetically Obese Rats

Radioactive iodine was released from the thyroid of genetically obese rats more slowly than from glands of lean or lesioned-obese rats. The uptake of radioiodine was also less in the genetically obese rats fed a low iodine diet, but not when the intake was high in iodine. Administration of exogenous TSH produced similar rates of release of radioactive iodine from the thyroids of lean and obese rats. The possibility of hypothalamic dysfunction in the genetically obese "fatty" rat was discussed. (Endocrinology 88: 1095, 1971) I 1961, Zucker and Zucker reported a strain of rats in which obesity is inherited as a mendelian recessive trait (1). Among the several defects which have been described in these rats (2) were hyperlipemia (3, 4) and a reduction in oxygen consumption (5). This latter observation led to the present studies of thyroid function of these animals. Materials and Methods Animals. Nineteen genetically obese female rats, 9 control obese rats and 16 lean female rats were used for these studies. Obesity developed in control rats following the introduction of bilateral electrolytic lesions of the hypothalamus, as described previously (6). All rats were maintained on Purina Laboratory Chow or on a low iodine diet (7) with tap water available ad lib. Procedures. Five experiments were performed. In the first experiment, 6 genetically obese rats and 6 lean litter mates were fed a low iodine diet for 14 days. Approximately 10 /*Ci of I was injected 24 hr before the experiment. Radioactivity remaining in the thyroid was assayed twice daily by placing the neck over a collimated well-type scintillation counter and recording 4000-10,000 counts. During the experiment, recycling of iodine was blocked by adding potassium perchlorate (1% w/v) to the drinking water. For the second experiment, 9 genetically obese, 6 lean and 5 lesioned rats were fed 14 g of food daily. Radioactive iodine uptake was determined twice, once on the chow diet and again after feeding a low iodine diet for 10 days. In the third experiment, 5 genetically obese and 5 lean litter mates were used. Twenty-four hr after injection of I, potassium perchlorate (1% w/v) Received May 11, 1970. Supported in part by Grants AM-9897 and AM05166 from the NIH. Reprint requests to: Dr. George Bray, 1000 W. Carson St., Torrance, Calif. 90509. 1 Genetic obese rats obtained from Dr. L. M. Zucker, Harriet G. Bird Memorial Laboratory, Stow, Mass. was added to the drinking water and each rat was started on a daily injection of 7.5 ng of thyroxine. After 4 daily neck counts, injections of thyrotropin, 300 mU/100 g/day, were given along with the thyroxine for an additional 4 days. The fourth experiment was performed on 4 genetically obese and 4 lesioned-obese rats fed chow diet. Measurements of uptake and release of I were performed as described for the first experiment. The fifth and final experiment utilized the same rats as the second experiment. A low iodine diet was fed ad lib. for 10 days. Twenty-four hr before sacrifice, each rat received 25 /xCi of I ip. Samples of blood were obtained from the abdominal aorta. The thyroid gland was dissected free, weighed, and the radioactivity measured with a well counter. Half of the thyroid was used for determination of total chemical iodine and the other half was homogenized and incubated with pronase overnight at 37 C. Aliquots of this digest were applied to strips of No. 3 Whatman filter paper and chromatographed in 2 systems (8). The strips were dried and the appropriate spots cut out and counted in a gamma counter. I-PBI was measured on § ml of the serum after 3 washes with 3 ml 10% TCA. The precipitate was then analyzed for PBI. Materials. Thyrotropin (Thytropar, Armour and Co., Chicago, 111.) was diluted in 0.15M saline. Thyroxine (Sigma, St. Louis, Mo.) was dissolved in 0.5N NaOH and then diluted in 0.15M saline. The low iodine diet (7) was purchased from Nutritional Biochemicals Co., Cleveland, Ohio. Calculations. Data are expressed as mean±SE. Analysis of variance, regression lines and correlation coefficients were determined using a desk top calculator.