Thyroid hormone-dependent regulation of metabolism and heart regeneration

Abstract

While adult zebrafish and newborn mice possess a robust capacity to regenerate their hearts, this ability is generally lost in adult mammals. The logic behind the diversity of cardiac regenerative capacity across the animal kingdom is not well understood. We have recently reported that animal metabolism is inversely correlated to the abundance of mononucleated diploid cardiomyocytes in the heart, which retain proliferative and regenerative potential. Thyroid hormones are classical regulators of animal metabolism, mitochondrial function, and thermogenesis and a growing body of scientific evidence demonstrates that these hormonal regulators also have direct effects on cardiomyocyte proliferation and maturation. We propose that thyroid hormones dually control animal metabolism and cardiac regenerative potential through distinct mechanisms, which may represent an evolutionary tradeoff for the acquisition of endothermy and loss of heart regenerative capacity. In this review, we describe the effects of thyroid hormones on animal metabolism and cardiomyocyte regeneration, and highlight recent reports linking the loss of mammalian cardiac regenerative capacity to metabolic shifts occurring after birth.

The origin, progress, and application of cell‐based cardiac regeneration therapy

“…To regenerate the heart, it needs more than 50% diploid cardiomyocytes (Lerchenmuller et al, 2022). Other studies confirm that the thyroid hormone through regulating metabolism influences the ploidy of myocardial cells and zebrafish with low thyroid hormone concentration so single‐core diploid myocardial cell abundance is high, when given exogenous thyroid hormone, zebrafish heart regeneration is restrained (Marshall et al, 2019; Ross et al, 2022), which is closely connected with the attribute of zebrafish cold‐blooded animals.…”

“…Both mitosis and multinucleation decreased rapidly after 1 week of birth, followed by polyploidy, and peaked at 14 days after birth (Pu et al, 2022). From another perspective, a week after the birth of newborn mice by variable temperature into warm‐blooded animals, thyroid hormone levels continue to increase, so the mice in obtaining heat production capacity at the same time, increase the content of the dual‐core polyploidy myocardial cells, and regeneration ability to drop, then make the conduction inactivation of thyroid hormones, myocardial cell polyploidy is restrained, the ability of the heart to regenerate is also preserved (Hirose et al, 2019; Ross et al, 2022). In general, the number of mouse cardiomyocytes is mostly the result of proliferation within the first week of life, polynucleation and nuclear polyploidy before puberty also contribute to nonreplicative DNA synthesis, and cardiac enlargement after puberty is mainly due to cardiac hypertrophy.…”

Unlocking cardiomyocyte renewal potential for myocardial regeneration therapy

“…Downstream target genes are subsequently expressed when ligand is bound to the receptor. These thyroid hormone-inducible genes have widespread functions in regulating metabolic balance and cell maturation [72][73][74][75].…”

“…Serum thyroid hormone levels are substantially lower in newts and zebrafish than in non-regenerative mammals, rising before birth in sheep and soon after birth in neonatal mice [43,76,77]. How thyroid hormones impact cardiomyocyte cell cycle activity and heart regeneration has been explored in certain vertebrate species [73,78,79]. Gerdes and colleagues investigated the consequence of T3 treatment in neonatal rats.…”

Transcriptomic, histological and biochemical analyses of Macrobrachium nipponense response to acute heat stress

“…2021). The synthesis of thyroid hormones promotes the metabolic level of the organism to help combat heat stress(Ross et al 2022). The extracellular matrix (ECM) affects ROS synthesis through integrins(Mlih and Karpac 2022).…”