Thyroid Hormones and Metabolism Regulation: Which Role on Brown Adipose Tissue and Browning Process?

Abstract

Thyroid hormones (THs) are important modulators of many metabolic processes, being strictly associated with the control of energy balance, mainly through activities on the brain, white and brown adipose tissue, skeletal muscle, liver, and pancreas. In this review, the principal mechanisms of TH regulation on metabolic processes will be discussed and THs' relevance in metabolic disease progression will be evaluated, especially in the cardiovascular context and correlated diseases. Moreover, we will discuss THs' regulatory role on metabolic events in white and brown adipose tissue, with a special focus on the process of "browning", which consists of the gradual acquisition by white adipocytes of the physical and functional characteristics of brown adipocytes. The advancements in research on molecular mechanisms and proposed physiopathological relevance of this process will be discussed.

Keywords: brown adipose tissue; browning; metabolism; thyroid hormones.

Figure 1

Pathways of outer and inner ring deiodination of thyroid hormones.

Figure 2

TH regulation of UCP1-dependent thermogenesis in BAT. Hypothalamus responds to stress signals rapidly releasing NE from terminal nerve of SNS present in BAT. NE stimulates β3-AR on adipocyte’s membrane, triggering a signaling cascade that leads to intracellular hydrolysis of TG, with consequent release of FAs. FAs, in turn, activate UCP1, which uncouples ATP production, and this causes release of energy as heat. Circulating THs enter the adipocytes through TH transporters in the cell membrane and T4 is converted into T3 by DIO2 enzyme. In the nucleus, upon binding TR, T3 stimulates UCP1 expression. In BAT, adrenergic and TH signaling coordinate to regulate UCP1 expression.