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Thyroid hormone receptor ? in skeletal muscle is essential for T3-mediated increase in energy expenditure.

ABSTRACT: Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole-body energy metabolism and body temperature has not been resolved. Here, we show that T3-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TR?1 ) in skeletal muscle, but that T3-mediated elevation in body temperature is achieved in the absence of muscle-TR?1 . In slow-twitch soleus muscle, loss-of-function of TR?1 (TR?HSACre ) alters the fiber-type composition toward a more oxidative phenotype. The change in fiber-type composition, however, does not influence the running capacity or motivation to run. RNA-sequencing of soleus muscle from WT mice and TR?HSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TR?1 -linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3-stimulated increase in whole-body energy expenditure.

SUBMITTER: Nicolaisen TS

PROVIDER: S-EPMC7702122 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Thyroid hormone receptor α in skeletal muscle is essential for T3-mediated increase in energy expenditure.

Nicolaisen Trine S TS Klein Anders B AB Dmytriyeva Oksana O Lund Jens J Ingerslev Lars R LR Fritzen Andreas M AM Carl Christian S CS Lundsgaard Anne-Marie AM Frost Mikkel M Ma Tao T Schjerling Peter P Gerhart-Hines Zachary Z Flamant Frederic F Gauthier Karine K Larsen Steen S Richter Erik A EA Kiens Bente B Clemmensen Christoffer C

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20200923 11

Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole-body energy metabolism and body temperature has not been resolved. Here, we show that T3-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα<sub>1</sub> ) in skeletal muscle, but that T3-mediated elevation in body temperatur ...[more]

PMID: 32969079

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Project description:KEY POINTS:Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP. Thyroid hormones are known regulators of adult metabolism and are important in driving several aspects of fetal development, including muscle fibre differentiation. Mitochondrial density and the abundance of mitochondrial membrane proteins in skeletal muscle increased during late gestation. However, mitochondrial functional capacity, measured as oxygen consumption rate, increased primarily after birth. Fetal hypothyroidism resulted in significant reductions in mitochondrial function and density in skeletal muscle before birth. Mitochondrial function matures towards birth and is dependent on the presence of thyroid hormones, with potential implications for the health of pre-term and hypothyroid infants. ABSTRACT:Birth is a significant metabolic challenge with exposure to a pro-oxidant environment and the increased energy demands for neonatal survival. This study investigated the development of mitochondrial density and activity in ovine biceps femoris skeletal muscle during the perinatal period and examined the role of thyroid hormones in these processes. Muscle capacity for oxidative phosphorylation increased primarily after birth but was accompanied by prepartum increases in mitochondrial density and the abundance of electron transfer system (ETS) complexes I-IV and ATP-synthase as well as by neonatal upregulation of uncoupling proteins. This temporal disparity between prepartum maturation and neonatal upregulation of mitochondrial oxidative capacity may protect against oxidative stress associated with birth while ensuring energy availability to the neonate. Fetal thyroid hormone deficiency reduced oxidative phosphorylation and prevented the prepartum upregulation of mitochondrial density and ETS proteins in fetal skeletal muscle. Overall, the data show that mitochondrial function matures over the perinatal period and is dependent on thyroid hormones, with potential consequences for neonatal viability and adult metabolic health.

Dataset Information

Thyroid hormone receptor ? in skeletal muscle is essential for T3-mediated increase in energy expenditure.

Publications

Thyroid hormone receptor α in skeletal muscle is essential for T3-mediated increase in energy expenditure.

Similar Datasets

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