热量限制是减重和治疗代谢性疾病的重要途径。然而，长期热量限制患者常出现T3水平降低、减重进入平台期，甚至体重反弹的现象，其机制不明。研究表明，热量限制所致脱碘酶D2表达下调、抑制T4向T3转换，是T3水平下降的主要原因。胆汁酸受体TGR5因具能量代谢调控功能，是目前研究的热点。新近研究提示，TGR5可诱导棕色脂肪D2表达。课题组前期研究发现，长期热量限制小鼠棕色脂肪TGR5表达明显下降，但其是否系长期热量限制所致T3降低的关键因素，是否对体重反弹产生影响，则需进一步探索。我们拟分别采用活体转染TGR5受体基因、高胆汁酸饮食等方式干预长期热量限制的肥胖小鼠，观察热量限制不同时期，小鼠棕色脂肪TGR5、D2和胞内T3的表达，甲状腺功能改变，以及棕色脂肪含量及活性的变化。从而明确TGR5在热量限制中所起的作用，为长期热量限制所致T3减低、体重反弹提供干预靶点。

Caloric restriction is an important way for treatment of metabolic diseases and weight loss. However, most patients may manifested with reduced triiodothyronine (T3), weight loss plateau, or even weight regain during long-term calorie restriction. The underlying mechanism of this phenomenon is unknown. Studies show that calorie restriction induced downregulation of type 2 deiodinase (D2) and inhibition of T4 conversion to T3 are the main reasons for T3 decrease. G protein-coupled receptor for bile acids (TGR5) has been proved to be involved in energy metabolism regulation. Recent studies suggest that TGR5 induced the expression of D2 in brown adipose tissue. Our previous studies also found that the expression of TGR5 in brown adipose tissue decreased significantly in mice under long-term caloric restriction. However, whether the decrease of TGR5 is a key factor for T3 reduction and whether it has an impact on weight regain under long-term calorie restriction, are need further exploration. Here we will use in vivo transfection of TGR5 gene, high bile acid diet to intervene long-term caloric restriction mice, observe the expression of TGR5, D2 and intracellular T3 in brown adipose tissue, detect thyroid function, the content and activity of brown adipose tissue during different period of calorie restriction. The results will explore the role of TGR5 in calorie restriction, and may provide the potential target for prevention of weight regain during long-term calorie restriction.