Thyroid hormones (THs) as a therapeutic intervention to treat obesity has been tried but the effect of THs on body weight and the mechanistic details of which are far from clear. This study was designed to determine and elucidate the mechanistic details of metabolic action of THs in high-fat diet (HFD) fed Sprague Dawley (SD) rats. Rats were made surgically hypothyroid (thyroidectomy, Thx). Body weights and food and water intake profoundly decreased in HFD fed thyroidectomized group (HN Thx). Results showed that delayed insulin response, increased total cholesterol, high-density lipoprotein, and low density lipoprotein in HN Thx. Unexpectedly, however, Thx reduced serum and hepatic triglyceride concentrations. Further studies revealed that Thx dramatically increased circulating GLP-1 as well as increased expressions of GLP-1 in small intestine. Diminished hepatic expressions of lipogenic genes, were observed in HN Thx group. Beta-catenin and glutamine synthetase, a known target of beta-catenin, were up-regulated in the liver of HN Thx group. The expressions of gluconeogenic genes G6P and PCK were reduced in the liver of HN Thx group. The results may suggest that surgery-induced hypothyroidism increases GLP-1, the actions of which may in part be responsible for the reduction in water intake, appetite and hepatic steatosis. (C) 2017 Elsevier Inc. All rights reserved.