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 (T3) may improve the low oxidative metabolism in metabolically important tissues of ob/ob mice. Triiodothyronine doses (2.5 to 25.0 micrograms/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 O2 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 O2 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 O2 consumption in non-ob/ob mice. In ob/ob mice, triiodothyronine increased only soleus muscle O2 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.