Development of compensatory thermogenesis in response to overfeeding in hypothyroid rats

Intact or surgically thyroidectomized (Tx) adult male Wistar rats, weighing 150-200 g, were fed a standard chow diet (similar to 1.8 Cal/g) or a high calorie (similar to 3.8 Cal/g) diet (cafeteria diet) for up to 30 days. Dai ly energy intake was about 5-fold higher in the rats fed the cafeteria diet regardless of their thyroid status. The cafeteria diet caused the retroper itoneal white fat pad to increase by approximately 2-fold, the volume of is olated white adipocytes to increase by 2-fold, and the total body fat to in crease by a factor of approximately 3, again regardless of thyroid status. It also increased basal metabolic rate by about 20% in intact rats and by a bout 50% in Tx rats. The brown fat thermal response to norepinephrine (NE) infusion was approximately 2-fold increased in the intact rats fed the cafe teria diet. However, in the Tx rats, the brown fat thermal response to NE w as blunted regardless of the dietary regimen adopted. In both intact and Tx rats, the cafeteria diet increased total brown fat mitochondria, uncouplin g protein percentage, and total brown fat uncoupling protein by about 3-, 2 -, and 5-fold, respectively. Serum leptin levels also increased approximate ly 4-fold in intact rats fed the cafeteria diet. However, in Tx rats, lepti n levels did not change significantly during overfeeding. In conclusion, hy pothyroidism caused the brown fat to become unresponsive to NE, even after 1 month on the cafeteria diet. However, these rats were able to increase ba sal metabolic rate and, as assessed by several different parameters, did no t gain fat beyond that observed in intact controls kept on a similar overfe eding schedule.