A TRbeta-selective agonist confers resistance to diet-induced obesity.
A TRbeta-selective agonist confers resistance to diet-induced obesity.
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DOI：
10.1677/joe-08-0539
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Ribeiro MO
中科院分区：
文献类型：
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作者：
Amorim BS;Ueta CB;Freitas BC;Nassif RJ;Gouveia CH;Christoffolete MA;Moriscot AS;Lancelloti CL;Llimona F;Barbeiro HV;de Souza HP;Catanozi S;Passarelli M;Aoki MS;Bianco AC;Ribeiro MO
甲状腺激素受体β（TR β在MGI数据库中也被列为THRB）-选择性激动剂激活棕色脂肪组织（BAT）产热，同时仅对心脏活动或瘦体重产生最小影响。在这里，我们测试了以下假设：每日给予TR β激动剂GC-24可预防与高热量饮食相关的代谢改变。将大鼠置于高脂饮食中，一个月后表现出体重（BW）和肥胖增加，空腹高血糖症和葡萄糖耐受不良，甘油三酯、胆固醇、非酯化脂肪酸和白细胞介素-6的血浆水平升高。虽然GC-24对这些动物的给药不影响食物摄入或改变BW增加的进展，但它确实增加了能量消耗，消除了肥胖的增加而不引起心脏肥大。空腹高血糖保持不变，但GC-24治疗通过增加胰岛素敏感性改善了葡萄糖耐量，并使血浆甘油三酯水平正常化。血浆胆固醇水平仅部分正常化，并且在GC-24处理的动物中肝脏胆固醇含量仍然很高。肝脏、骨骼肌和白色脂肪组织中的基因表达仅受到GC-24处理的最小影响，主要靶点是BAT。总之，在用TR β选择性激动剂进行高脂喂养处理期间，GC-24仅部分改善代谢控制，这可能是由于加速了静息代谢率。
Thyroid hormone receptor β (TRβ also listed as THRB on the MGI Database)-selective agonists activate brown adipose tissue (BAT) thermogenesis, while only minimally affecting cardiac activity or lean body mass. Here, we tested the hypothesis that daily administration of the TRβ agonist GC-24 prevents the metabolic alterations associated with a hypercaloric diet. Rats were placed on a high-fat diet and after a month exhibited increased body weight (BW) and adiposity, fasting hyperglycemia and glucose intolerance, increased plasma levels of triglycerides, cholesterol, nonesterified fatty acids and interleukin-6. While GC-24 administration to these animals did not affect food ingestion or modified the progression of BW gain, it did increase energy expenditure, eliminating the increase in adiposity without causing cardiac hypertrophy. Fasting hyperglycemia remained unchanged, but treatment with GC-24 improved glucose tolerance by increasing insulin sensitivity, and also normalized plasma triglyceride levels. Plasma cholesterol levels were only partially normalized and liver cholesterol content remained high in the GC-24-treated animals. Gene expression in liver, skeletal muscle, and white adipose tissue was only minimally affected by treatment with GC-24, with the main target being BAT. In conclusion, during high-fat feeding treatment with the TRβ-selective agonist, GC-24 only partially improves metabolic control probably as a result of accelerating the resting metabolic rate.