The 3,5-diiodo-L-thyronine (3,5-T2) is an endogenous metabolite of thyroid hormones, whose administration to rodents fed high-fat diet (HFD) prevents body weight increase and reverts the expression pattern of pro-inflammatory factors associated to HFD. The diet-induced obese (D.I.O.) zebrafish (Danio rerio) has been recently used as an experimental model to investigate fundamental processes underlying central and peripheral obesity-driven inflammation. Herein, we aim to understand the role of 3,5-T2 in regulating central and peripheral inflammation in D.I.O. model of zebrafish. 3,5-T2 (10 nM and 100 nM) was administered with the obesity-inducing diet (D.I.O. with 3,5-T2) or after 4 weeks of obesity-inducing diet (D.I.O. flw 3,5-T2). 3,5-T2 significantly increased the body weight and serum triglyceride levels in D.I.O. zebrafish in both conditions. Moreover, 3,5-T2 sustained or increased inflammation in the anterior (AI) and mid (MI) intestine when administered with the obesity-inducing diet, as indicated by the immunoexpression of the inflammatory markers tumor-necrosis factor-α (TNFα), cyclooxygenase 2 (COX2), calnexin, caspase 3, and proliferating cell nuclear antigen (PCNA). On the contrary, when 3,5-T2 was administered after the obesity-inducing diet, partly reverted the intestinal alteration induced by D.I.O. In addition, brain inflammation, as indicated by the increase in the activation of microglia, was detected in D.I.O. zebrafish and D.I.O. treated with 3,5-T2. These findings reveal that the effects of 3,5-T2 on fish intestine and brain can deviate from those shown in obese mammals, opening new avenues to the investigation of the potential impact of this thyroid metabolite in different diseases including obesity.

中文翻译：

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3,5-T2处理的肥胖动物模型（Danio rerio）肠道和中枢神经系统形态的免疫组织化学分析：可能的农场管理方法？

3,5-二碘-L-甲状腺素（3,5-T2）是甲状腺激素的内源性代谢产物，对高脂饮食（HFD）喂养的啮齿类动物给药可防止体重增加并逆转促炎的表达模式与HFD相关的因素。饮食诱发的肥胖（DIO）斑马鱼（Danio rerio）最近已用作实验模型，以研究中枢和外周肥胖驱动的炎症的基本过程。在本文中，我们旨在了解3,5-T2在调节斑马鱼DIO模型中的中枢和外周炎症中的作用。3,5-T2（10 nM和100 nM）与肥胖诱导饮食（含3,5-T2的DIO）一起服用，或在肥胖诱导饮食4周后（DIO 3,5-T2）服用。在这两种情况下，3,5-T2均可显着增加DIO斑马鱼的体重和血清甘油三酯水平。此外，当通过肥胖诱导饮食给药时，3,5-T2在前（AI）和中（MI）肠中持续或增加炎症，如炎症标志物肿瘤坏死因子-α（TNFα）的免疫表达所表明，环氧合酶2（COX2），钙粘蛋白，胱天蛋白酶3和增殖细胞核抗原（PCNA）。相反，在肥胖诱导饮食后施用3,5-T2时，可部分恢复DIO引起的肠道改变。此外，在DIO斑马鱼和DIO用3,5-T2处理。这些发现表明，3,5-T2对鱼肠和大脑的影响可能与肥胖哺乳动物中显示的有所不同，