Non-classic thyroid hormone signalling involved in hepatic lipid metabolism

Abstract

Thyroid hormones are important modulators of lipid metabolism because the liver is a primary hormonal target. The hypolipidaemic effects of thyroid hormones result from the balance between direct and indirect actions resulting in stimulation of lipid synthesis and lipid oxidation, which favours degradation pathways. Originally, it was believed that thyroid hormone activity was only transduced by alteration of gene transcription mediated by the nuclear receptor thyroid hormone receptors, comprising the classic action of thyroid hormone. However, the discovery of other effects independent of this classic mechanism characterised a new model of thyroid hormone action, the non-classic mechanism that involves other signalling pathways. To date, this mechanism and its relevance have been intensively described. Considering the increasing evidence for non-classic signalling of thyroid hormones and the major influence of these hormones in the regulation of lipid metabolism, we reviewed the role of thyroid hormone in cytosolic signalling cascades, focusing on the regulation of second messengers, and the activity of effector proteins and the implication of these mechanisms on the control of hepatic lipid metabolism.

(Healthy) Ageing: Focus on Iodothyronines

“…Nuclear TRβ protein levels decrease in both of those organs with age, whereas nuclear TRα1 levels are unaltered. Notably, the same authors showed that total cellular TRβ protein levels increase during ageing in both liver and kidney (in the latter, TRα protein also increases), which might suggest that certain extra-nuclear non-genomic actions, several of which being reported to depend on TRs [13,14,22,24] are more pronounced during ageing. However, to our knowledge no information exists in the literature on this subject.…”

“…In recent years, thyroid hormone and its metabolites have been shown to have non-genomic effects too, via actions at the level of the cell membrane [13], the cytosol [14–17], the mitochondrion [18–20], or the nucleus [21,22]. Many aspects of the genomic and non-genomic actions of thyroid hormones have been reviewed elsewhere [1,12,13,23,24]. For clarity, the following sections of this review will deal only with the newly emerging thyroid hormone-related mechanisms involving factors related to the ageing process (such as sirtuin1 (SIRT1) and AMP-activated protein kinase (AMPK)).…”

Recent advances in physiological lipoprotein metabolism

“…ANGPTL3 gene is negatively regulated by triodothyronine leading to the speculation that triodothyronine can lower plasma triglycerides by suppressing the ANGPTL3 gene thus activating LPL which plays a central role in lipid metabolism [317]. Thyroid hormone interaction with the nuclear thyroid hormone receptor accounts for several of the lipid reduction effects by thyroid hormones, though recent work suggests that non-classic mechanism involving cytosolic second messengers including calcium and phosphoinositide-3-kinase, could contribute to the effect of thyroid hormones on lipid homeostasis [318].…”

Does closantel in therapeutic doses display thyroid hormone‐like activity in sheep?

“…On the other hand, a positive correlation was described between TSH concentration and triglycerides in human, although T4 correlated inversely (Nader et al ., ). Thyroid function is, among other activities, associated with lipid metabolism (Erem et al ., ; Pucci et al ., ; Cordeiro et al ., ); however, no direct connection between elevated triglycerides and thyroid hormone‐like activity of closantel was evident in this study.…”