EARLY TREATMENT OF OBESE (OB/OB) MICE WITH TRIIODOTHYRONINE INCREASES OXIDATIVE-METABOLISM IN MUSCLE BUT NOT IN BROWN ADIPOSE-TISSUE OR LIVER

We explored the possibility that early replacement of low triiodothyronine (T-3) may improve the low oxidative metabolism in metabolically important tissues of ob/ob mice. Triiodothyronine doses (2.5 to 25.0 mu g/100 g body wt) were injected intraperitoneally into ob/ob and non-ob/ob mice daily from 3 wk until 6 wk of age. Untreated ob/ob and non-ob/ob mice were injected with saline (pH 9.1). Food intake was equalized across all groups. At 6 wk of age, the O-2 consumption of muscle, white and brown adipose tissues, and hepatocytes was measured. The saline-treated ob/ob mice showed lower muscle weights, higher fat pad and liver weights, and larger fat cell sizes than saline-treated non-ob/ob mice. In ob/ob mice, tissue O-2 consumption was the same in muscle, lower in brown and white adipose tissues, but higher in liver compared with values in non-ob/ob mice. Triiodothyronine treatment in ob/ob mice resulted in lower values for body weight, liver weight, hepatocyte number, liver protein, epididymal fat pad weight, and white adipocyte number and size than in saline-treated ob/ob mice. Triiodothyronine treatment increased soleus muscle, liver and brown adipose tissue O-2 consumption in non-ob/ob mice. In ob/ob mice, triiodothyronine increased only soleus muscle O-2 consumption and required higher doses than in non-ob/ob mice to achieve an effect. These data are consistent with the concept of tissue triiodothyronine resistance in ob/ob mice. Low triiodothyronine levels and tissue resistance to triiodothyronine might be important early defects in this obesity syndrome.