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Early Treatment of Obese (ob/ob) Mice with Triiodothyronine Increases Oxidative Metabolism in Muscle but not in Brown Adipose Tissue or Liver^1,2,

Food Science and Human Nutrition Department, Iowa State University, Ames, IA 50011

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 µg/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.

KEY WORDS: • ob/ob mice • triiodothyronine • obesity • oxidative metabolism

¹ Supported by the Iowa Agriculture and Home Economics Experiment Station, project no. 3158. Journal paper no. J-15576 of the Iowa Agriculture and Home Economics Experiment Station.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 13 October 1993. Revision accepted 12 July 1994.