Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli Caserta, Italy.
Front Physiol. 2014 Dec 5;5:475. doi: 10.3389/fphys.2014.00475. eCollection 2014.
Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3'-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through "non-genomic" pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.
体重减轻是通过负能平衡实现的，这是对抗肥胖和 2 型糖尿病的目标。甲状腺通过甲状腺激素（TH）的作用，是能量代谢的重要调节剂。经典的、活跃的 TH，3,5,3'-三碘-L-甲状腺素（T3）主要通过与核受体（称为 TH 受体（TRs））结合来发挥作用，这些受体识别 DNA 上的 TH 反应元件（TREs），从而调节转录。T3 还通过不涉及 TRs 的“非基因组”途径发挥作用。降脂治疗被认为具有潜在的益处，然而，全面的治疗策略仍有待建立。在对抗肥胖中使用 T3 的一个缺点是出现心律不齐。这些是通过一种称为 TRα 的 TR 介导的。上世纪末，人们探索了 TH 拟似物，这些拟似物专门与 TRβ结合，以防止心脏紊乱，以及具有有趣生物学活性的 TH 衍生物，如 3,5-二碘-L-甲状腺素（T2）。几种 TH 衍生物和功能类似物对 TR 的亲和力较低，被认为主要通过非基因组途径发挥作用。所有这些都为甲状腺生理学和 TH 衍生物作为抗肥胖疗法的应用开辟了新的前景。鉴于这些化合物对能量平衡调节和脂质/胆固醇代谢的影响，本文综述了这些化合物的优缺点。
