Proteomic approaches for the study of tissue specific effects of 3,5,3'-triiodo-L-thyronine and 3,5-diiodo-L-thyronine in conditions of altered energy metabolism

Abstract

In vertebrates and, specifically, in mammals, energy homeostasis is achieved by the integration of metabolic and neuroendocrine signals linked to one another in an intricate network hierarchically responding to the tight modulating action of hormones among which thyroid hormones (THs) play a central role. At the cellular level, 3,5,3'-triiodo-L-thyronine (T3) acts mainly by binding to specific nuclear receptors (TRs) but actually it is becoming more and more evident that some T3- actions are independent of TRs and that other iodothyronines, such as 3,5-diiodo-L-thyronine (T2), affect energy metabolism and adiposity. In the postgenomic era, clinical and basic biological researches are increasingly benefiting from the recently developed new omics approaches including, among the others, proteomics. Considering the recognized value of proteins as excellent targets in physiology, the functional and simultaneous analysis of the expression level and the cellular localization of multiple proteins can actually be considered fundamental in the understanding of complex mechanisms such as those involved in thyroid control of metabolism. Here, we will discuss new leads (i.e., target proteins and metabolic pathways) emerging in applying proteomics to the actions of T3 and T2 in conditions of altered energy metabolism in animal tissues having a central role in the control of energy balance.

Keywords: iodothyronine; metabolism; mitochondrion; obesity; proteomics.

Figure 1

Synoptic of the workflow of the proteomic approaches so far utilized to obtain new information on the actions that T2 and T3 exert in vivo in key metabolically active tissues central in the control of energy balance. The described studies were performed as integrated approaches including 2D-E, mass spectrometry, and bioinformatic tools (Silvestri et al., , , ; Moreno et al., 2011). Abbreviations: N, standard diet fed control rats; HFD, high fat diet fed rats; HFD+T2, high fat diet fed rats treated with T2; Eu, euthyroid rats; Hypo, hypothyroid rats; Hypo+T3, hyperthyroid rats.