A Direct Comparison of Thyroid Hormone Receptor Protein Levels in Mice Provides Unexpected Insights into Thyroid Hormone Action

Minakhina, Svetlana; Bansal, Sanya; Zhang, Alice; Brotherton, Michael; Janodia, Rucha; Oliveira, Vanessa De; Tadepalli, Srikanth; Wondisford, Fredric E.

doi:10.1089/thy.2019.0763

Cited by 39 publications

(63 citation statements)

References 65 publications

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“…24,25 A recent study convincingly confirmed this using in vivo HA-tag insertions and antibodies for HA-tagged versions of TRα 1, TRα 2 and TRβ. 8 They demonstrated-at the protein level-that TRα 1 is the predominant thyroid hormone receptor in skeletal muscle. Functionally, this is supported by global thyroid hormone receptor KO studies showing that deletion of TRα 1 leads to a lower abundance of fast-twitch fibers in SOL and that ablation of TRβ has no consequences on muscle morphology.…”

Section: Discussionmentioning

confidence: 99%

“…In skeletal muscle, TRα 1 is the primary receptor, 8 and to resolve whether thyroid hormone action in muscle is necessary for thyroid hormone‐mediated increase in energy expenditure and the associated increase in body temperature, we developed a skeletal muscle‐specific TRα 1 ‐dominant negative mouse model (TRα 1 loss‐of‐function). Notably, we discovered that under both normal and metabolically compromised conditions, T3‐mediated increase in whole‐body energy expenditure, in part, relies on TRα 1 signaling in skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…While this was found to be dependent on TRα1, other studies observed an important role of TRβ in the VMH in this context, although BAT function specifically was not studied in great detail ( 57 ). However, given that TRα1 is the predominant isoform in neurons ( 58 ) and the levels of hypothalamic TRβ protein are low ( 59 ), the precise contribution of TRβ to the central control of BAT thermogenesis remains yet to be established in this context.…”

Section: Central Effects Of Thmentioning

confidence: 99%

Thyroid hormones in the regulation of brown adipose tissue thermogenesis

Sentis

Oelkrug

Mittag

2021

Endocrine Connections

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A normal thyroid status is crucial for body temperature homeostasis, as thyroid hormone regulates both heat loss and conservation as well as heat production in thermogenic tissues. Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis and an important target of thyroid hormone action. Thyroid hormone not only regulates the tissue’s sensitivity to sympathetic stimulation by norepinephrine, but also the expression of uncoupling protein 1, the key driver of BAT thermogenesis. Vice versa, sympathetic stimulation of BAT triggers the expression of deiodinase type II, an enzyme that enhances local thyroid hormone availability and signaling. This review summarizes the current knowledge on how thyroid hormone controls BAT thermogenesis, aiming to dissect the direct actions of the hormone in BAT and its indirect actions via the central nervous system, browning of white adipose tissue or heat loss over body surfaces. Of particular relevance is the apparent dose dependency of the observed effects, as we find that minor or moderate changes in thyroid hormone levels often have different effects as compared to high pharmacological doses. Moreover, we conclude that the more recent findings require a reevaluation of older studies, as key aspects such as heat loss or central BAT activation may not have received the necessary attention during the interpretation of these early findings. Finally, we provide a list of what we believe are the most relevant questions in the field that to date are still enigmatic and require further studies.

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“…Meanwhile, the results of network pharmacology indicated that THRA and THRB might be potential therapeutic targets for hypothyroidism. THRA1, THRB1 and THRB2 were three major thyroid hormone receptors and mediated thyroid hormone actions, which were encoded by THRA and THRB (Minakhina et al, 2020). THRA and THRB mutations directly caused abnormal thyroid hormone levels, which was associated with tissue-specific hypothyroidism (Schoenmakers, 2012).…”

Section: Thyroid Hormone Signaling Pathwaymentioning

confidence: 99%

Application of Proteomics and Metabonomics to Reveal the Molecular Basis of Atractylodis Macrocephalae Rhizome for Ameliorating Hypothyroidism Instead of Hyperthyroidism

et al. 2021

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As the treatments of diseases with Chinese herbs are holistic and characterized by multiple components, pathways, and targets, elucidating the efficacy of Chinese herbs in treating diseases, and their molecular basis, requires a comprehensive, network-based approach. In this study, we used a network pharmacology strategy, as well as in vivo proteomics and metabonomics, to reveal the molecular basis by which Atractylodis macrocephalae rhizome (AMR) ameliorates hypothyroidism. Eighteen main compounds from AMR and its fractions (volatile oil fraction, crude polysaccharides fraction, lactones fraction, oligosaccharide fraction, and atractyloside fraction) were identified by HPLC, and their targets were screened using the TCMSP database and Swiss Target Prediction. Disease targets were gathered from the TTD, CTD and TCMSP databases. Hub targets were screened by different plug-ins, such as Bisogene, Merge, and CytoNCA, in Cytoscape 3.7.1 software and analyzed for pathways by the DAVID database. Hypothyroidism and hyperthyroidism pharmacological models were established through systems pharmacology based on proteomic and metabolomic techniques. Finally, AMR and its fractions were able to ameliorate the hypothyroidism model to different degrees, whereas no significant improvements were noted in the hyperthyroidism model. The lactones fraction and the crude polysaccharides fraction were considered the most important components of AMR for ameliorating hypothyroidism. These amelioration effects were achieved through promoting substance and energy metabolism. In sum, the integrative approach used in this study demonstrates how network pharmacology, proteomics, and metabolomics can be used effectively to elucidate the efficacy, molecular basis, and mechanism of action of medicines used in TCM.

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A Direct Comparison of Thyroid Hormone Receptor Protein Levels in Mice Provides Unexpected Insights into Thyroid Hormone Action

Cited by 39 publications

References 65 publications

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

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

Thyroid hormones in the regulation of brown adipose tissue thermogenesis

Application of Proteomics and Metabonomics to Reveal the Molecular Basis of Atractylodis Macrocephalae Rhizome for Ameliorating Hypothyroidism Instead of Hyperthyroidism

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