The effect of thyroid-stimulating hormone receptor (TSHR) on hepatic lipid accumulation in vivo is not fully understood. Further, while TSHR in the thyroid has been studied extensively, whether and how the absence of TSHR in the liver affects systemic energy metabolism has not yet been reported. To examine these effects, we generated hepatic TSHR conditional knockout (LT-KO) mice using Cre/LoxP recombination technology. The liver-specific TSHR-knockout (LT-KO) mice exhibited not only lower hepatic triglyceride and cholesterol contents due to modified synthesis and catabolism of lipids in the liver, but also decreased serum lipids, especially serum LDL-C levels. Abnormalities of TSHR in the thyroid affect whole body energy balance; however, measurements taken in metabolic chambers showed that the hepatic TSHR conditional deletion had no impact on systemic energy metabolism. Unlike its critical role in maintaining the normal growth and function of the thyroid gland, our results demonstrated that hepatic TSHR is involved in liver lipid metabolism and has little effect on energy metabolism. (C) 2018 Elsevier Inc. All rights reserved.