Abstract
3,5,3′-Triiodo-L-thyronine (T3) plays a crucial role in regulating metabolic rate and fuel oxidation; however, the mechanisms by which it affects whole-body energy metabolism are still not completely understood. Skeletal muscle (SKM) plays a relevant role in energy metabolism and responds to thyroid state by remodeling the metabolic characteristics and cytoarchitecture of myocytes. These processes are coordinated with changes in mitochondrial content, bioenergetics, substrate oxidation rate, and oxidative phosphorylation efficiency. Recent data indicate that “emerging” iodothyronines have biological activity. Among these, 3,5-diiodo-L-thyronine (T2) affects energy metabolism, SKM substrate utilization, and mitochondrial functionality. The effects it exerts on SKM mitochondria involve more aspects of mitochondrial bioenergetics; among these, respiratory chain activity, mitochondrial thermogenesis, and lipid-handling are stimulated rapidly. This mini review focuses on signaling and biochemical pathways activated by T3 and T2 in SKM that influence the above processes. These novel aspects of thyroid physiology could reveal new perspectives for understanding the involvement of SKM mitochondria in hypo- and hyper-thyroidism.
Highlights
Skeletal muscle (SKM) is a metabolically active tissue representing about 40% of total body mass
The present mini review provides an overview of the involvement of SKM mitochondria in T3 and/or T2 effects exerted on modulation of SKM metabolism/plasticity
Alterations in thyroid state are associated with changes in energy demand, with SKM adapting its metabolism by modulating substrate utilization
Summary
Skeletal muscle (SKM) is a metabolically active tissue representing about 40% of total body mass. It significantly affects energy expenditure and plays a significant role in glucose, lipid, and energy homeostasis. SKM shows a remarkable plasticity in functional adaptation and remodeling in response to physiological stimuli, such as exercise, fasting, and hormonal signals. SKM responds to variations in thyroid state by coordinately remodeling its cytoarchitecture and metabolic characteristics, with mitochondria playing a significant role. Concerning metabolic adaptations, T3 enhances the use of lipids and carbohydrates as fuel substrates (de Lange et al, 2008; Lombardi et al, 2012), as well as alteration of mitochondrial number and functionality
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