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Regulation of skeletal muscle mitochondrial activity by thyroid hormones: focus on the "old" triiodothyronine and the "emerging" 3,5-diiodothyronine.

Lombardi A, Moreno M, de Lange P, Iossa S, Busiello RA, Goglia F - Front Physiol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Naples Federico II Naples, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of signaling and biochemical pathways activated by T3 and/or T2 in skeletal muscle that promote variations in substrate metabolism, lipid handling, and thermogenesis at the mitochondrial level. If not accompanied by T3 or T2, the symbol + indicates that the pathway is stimulated by both iodothyronines. T3 and T2 activate processes leading to the import of FFA and their oxidation at the mitochondrial level, with FAT/CD36 playing a role. Through activation of AMPK-ACC signaling pathway, T2 and T3 relieves the inhibition of CPT1 by malonyl-CoA, and thus promote the entrance of fatty acids into mitochondria and their oxidation. The rise in MTE activity, would contribute to maintain a high level of fatty acid oxidation rate. The box represents processes, occurring at the level of mitochondrial inner membrane, underlying coupled and uncoupled respiration affected by T3 and T2.
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Figure 2: Schematic representation of signaling and biochemical pathways activated by T3 and/or T2 in skeletal muscle that promote variations in substrate metabolism, lipid handling, and thermogenesis at the mitochondrial level. If not accompanied by T3 or T2, the symbol + indicates that the pathway is stimulated by both iodothyronines. T3 and T2 activate processes leading to the import of FFA and their oxidation at the mitochondrial level, with FAT/CD36 playing a role. Through activation of AMPK-ACC signaling pathway, T2 and T3 relieves the inhibition of CPT1 by malonyl-CoA, and thus promote the entrance of fatty acids into mitochondria and their oxidation. The rise in MTE activity, would contribute to maintain a high level of fatty acid oxidation rate. The box represents processes, occurring at the level of mitochondrial inner membrane, underlying coupled and uncoupled respiration affected by T3 and T2.

Mentions: T3 affects both basal (Lombardi et al., 2012) and inducible SKM proton-leak (Lanni et al., 1999; Silvestri et al., 2005; Lombardi et al., 2012), with UCP3 and ANT being involved in the effects on free fatty acid (FA)-inducible proton-leak (Figure 2). In the transition between hypo- and hyper-thyroidism, the contribution of ANT to FA-induced uncoupling becomes progressively more relevant despite there being no variation in ANT-1 mRNA levels detected (Dümmler et al., 1996; Lombardi et al., 2002). This could be attributed to the gradual increase in mitochondrial SKM FA levels (Lombardi et al., 2002), known activators of ANT-mediated uncoupling (Skulachev, 1991). Concerning UCP3, T3 increases its transcription (Lanni et al., 1999; Barbe et al., 2001), the effect being observed within 8 h of T3 administration to hypothyroid rats (de Lange et al., 2001, 2007). The mechanism of UCP3 promoter stimulation by T3 seems to be species-specific since it involves FA and their target receptors (PPARδ) in humans and rats but not mice (de Lange et al., 2007).


Regulation of skeletal muscle mitochondrial activity by thyroid hormones: focus on the "old" triiodothyronine and the "emerging" 3,5-diiodothyronine.

Lombardi A, Moreno M, de Lange P, Iossa S, Busiello RA, Goglia F - Front Physiol (2015)

Schematic representation of signaling and biochemical pathways activated by T3 and/or T2 in skeletal muscle that promote variations in substrate metabolism, lipid handling, and thermogenesis at the mitochondrial level. If not accompanied by T3 or T2, the symbol + indicates that the pathway is stimulated by both iodothyronines. T3 and T2 activate processes leading to the import of FFA and their oxidation at the mitochondrial level, with FAT/CD36 playing a role. Through activation of AMPK-ACC signaling pathway, T2 and T3 relieves the inhibition of CPT1 by malonyl-CoA, and thus promote the entrance of fatty acids into mitochondria and their oxidation. The rise in MTE activity, would contribute to maintain a high level of fatty acid oxidation rate. The box represents processes, occurring at the level of mitochondrial inner membrane, underlying coupled and uncoupled respiration affected by T3 and T2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543916&req=5

Figure 2: Schematic representation of signaling and biochemical pathways activated by T3 and/or T2 in skeletal muscle that promote variations in substrate metabolism, lipid handling, and thermogenesis at the mitochondrial level. If not accompanied by T3 or T2, the symbol + indicates that the pathway is stimulated by both iodothyronines. T3 and T2 activate processes leading to the import of FFA and their oxidation at the mitochondrial level, with FAT/CD36 playing a role. Through activation of AMPK-ACC signaling pathway, T2 and T3 relieves the inhibition of CPT1 by malonyl-CoA, and thus promote the entrance of fatty acids into mitochondria and their oxidation. The rise in MTE activity, would contribute to maintain a high level of fatty acid oxidation rate. The box represents processes, occurring at the level of mitochondrial inner membrane, underlying coupled and uncoupled respiration affected by T3 and T2.
Mentions: T3 affects both basal (Lombardi et al., 2012) and inducible SKM proton-leak (Lanni et al., 1999; Silvestri et al., 2005; Lombardi et al., 2012), with UCP3 and ANT being involved in the effects on free fatty acid (FA)-inducible proton-leak (Figure 2). In the transition between hypo- and hyper-thyroidism, the contribution of ANT to FA-induced uncoupling becomes progressively more relevant despite there being no variation in ANT-1 mRNA levels detected (Dümmler et al., 1996; Lombardi et al., 2002). This could be attributed to the gradual increase in mitochondrial SKM FA levels (Lombardi et al., 2002), known activators of ANT-mediated uncoupling (Skulachev, 1991). Concerning UCP3, T3 increases its transcription (Lanni et al., 1999; Barbe et al., 2001), the effect being observed within 8 h of T3 administration to hypothyroid rats (de Lange et al., 2001, 2007). The mechanism of UCP3 promoter stimulation by T3 seems to be species-specific since it involves FA and their target receptors (PPARδ) in humans and rats but not mice (de Lange et al., 2007).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Naples Federico II Naples, Italy.

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.

No MeSH data available.


Related in: MedlinePlus