Regulation of iodothyronine 5'-deiodination in lean and obese (ob/ob) mice.

Abstract

Obese (ob/ob) mice exhibit impaired cold- and diet-induced thermogenesis, which may result in part from a defect in thyroid hormone action at the level of peripheral deiodination of thyroxine (T4) to 3,5,3'-triiodothyronine (T3). The latter possibility was examined by comparing kinetic parameters of 5'-deiodination (5'-D) in hepatic and renal microsomes of lean and obese mice during various physiological conditions. 5'-D Was adaptive to changes in age (1 to 8-10 wk), environmental temperature (14, 25, and 33 degrees C), and thyroid hormone status in both lean and obese mice. The magnitude of enzyme response, however, varied between phenotypes. 5'-D Response to age and environmental temperature was also dependent on tissue type, indicating that different isozymes for 5'-D may exist in liver and kidney. Under basal conditions at 25 degrees C, maximal hepatic and renal 5'-D was lower in obese mice than in lean mice. Differences in Vmax were observed as early as 1 wk of age. Km values for 5'-D were similar in lean and obese mice. These findings suggest that T3 availability to thermogenic target tissues may be impaired in obese mice, which may contribute to diminished thyroid hormone expression and heat production in these animals.