Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption

Johann, Kornelia; Cremer, Anna Lena; Fischer, Alexander W.; Heine, Markus; Pensado, Eva Rial; Resch, Julia; Nock, Sebastian; Virtue, Samuel; Harder, Lisbeth; Oelkrug, Rebecca; Astiz, Mariana; Brabant, Georg; Warner, Amy; Vidal-Puig, António; Oster, Henrik; Boelen, Anita; López, Miguel; Heeren, Joerg; Dalley, Jeffrey W.; Backes, Heiko; Mittag, Jens

doi:10.1016/j.celrep.2019.05.054

Cited by 84 publications

(131 citation statements)

References 86 publications

(121 reference statements)

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“…This is perhaps surprising given the increased focus on thyroid hormones and BAT thermogenesis over the last decade, yet, it aligns with recent studies showing that thyroid thermogenesis is intact in UCP1 KO mice. 6,7 Here, we demonstrate that T3-mediated elevation in whole-body energy expenditure can be ascribed, in part, to actions in muscle. Because the indirect calorimetry studies of the present study were executed at ambient temperature (22°C), a partially retained thermogenic capacity in BAT might contribute to the quantity of muscle-independent thermogenesis observed in the T3-treated TRα HSACre mice.…”

Section: Discussionmentioning

confidence: 66%

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: 66%

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

et al. 2020

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“…The discrepancy between GC-1 and TH effects on the BAT suggests that there may be potential differences in BAT activation and browning between TH and some of its analogs. TH also induced TRβ-mediated browning in the inguinal WAT, although the induction of browning did not increase glucose or triglyceride-rich protein uptake at thermoneutrality [104]. These data suggesting TRβ-selective GC-1-activated browning of the WAT and thermogenesis are difficult to reconcile with the TRα KO data showing that lack of functional TRα impaired thermogenesis during cold exposure.…”

Section: Th Induces Browning/beiging In Watmentioning

confidence: 77%

“…A conjugate of T 3 and glucagon, which selectively targets the WAT and liver, was able to induce browning in the WAT [103]. Mice rendered hyperthyroid showed an increased expression of BAT markers in their subcutaneous WAT after 3-4 weeks [53,104]. Moreover, subcutaneous administration of T 4 for 3 weeks induced Ucp1, Pgc1α, Cidea, Prdm16 mRNA expression in the gonadal and subcutaneous WAT in rats [37].…”

Section: Th Induces Browning/beiging In Watmentioning

confidence: 99%

Thermogenesis in Adipose Tissue Activated by Thyroid Hormone

Yau

Yen

2020

IJMS

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Thermogenesis is the production of heat that occurs in all warm-blooded animals. During cold exposure, there is obligatory thermogenesis derived from body metabolism as well as adaptive thermogenesis through shivering and non-shivering mechanisms. The latter mainly occurs in brown adipose tissue (BAT) and muscle; however, white adipose tissue (WAT) also can undergo browning via adrenergic stimulation to acquire thermogenic potential. Thyroid hormone (TH) also exerts profound effects on thermoregulation, as decreased body temperature and increased body temperature occur during hypothyroidism and hyperthyroidism, respectively. We have termed the TH-mediated thermogenesis under thermoneutral conditions “activated” thermogenesis. TH acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein (Ucp1) to generate heat. TH acts centrally to activate the BAT and browning through the sympathetic nervous system. However, recent studies also show that TH acts peripherally on the BAT to directly stimulate Ucp1 expression and thermogenesis through an autophagy-dependent mechanism. Additionally, THs can exert Ucp1-independent effects on thermogenesis, most likely through activation of exothermic metabolic pathways. This review summarizes thermogenic effects of THs on adipose tissues.

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“…The authors of this study speculate that this facultative endothermy is coupled to seasonal surges in hormones 'with pyrogenic potential' like thyroid. Intriguingly, thyroid hormone regulates expression of Ca 2+ -handling genes in muscle and has been suggested to recruit muscle NST [2,31,[104][105][106]. It is also interesting to note that several lizards possess the SLN gene which is highly conserved (figure 1).…”

Section: (C) Sarcolipin-based Non-shivering Thermogenesis During Vertmentioning

confidence: 99%

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

Bal

Periasamy

2020

Phil. Trans. R. Soc. B

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Thermogenesis in endotherms relies on both shivering and non-shivering thermogenesis (NST). The role of brown adipose tissue (BAT) in NST is well recognized, but the role of muscle-based NST has been contested. However, recent studies have provided substantial evidence for the importance of muscle-based NST in mammals. This review focuses primarily on the role of sarcoplasmic reticulum (SR) Ca 2+ -cycling in muscle NST; specifically, it will discuss recent data showing how uncoupling of sarcoendoplasmic reticulum calcium ATPase (SERCA) (inhibition of Ca 2+ transport but not ATP hydrolysis) by sarcolipin (SLN) results in futile SERCA pump activity, increased ATP hydrolysis and heat production contributing to muscle NST. It will also critically examine how activation of muscle NST can be an important factor in regulating metabolic rate and whole-body energy homeostasis. In this regard, SLN has emerged as a powerful signalling molecule to promote mitochondrial biogenesis and oxidative metabolism in muscle. Furthermore, we will discuss the functional interplay between BAT and muscle, especially with respect to how reduced BAT function in mammals could be compensated by muscle-based NST. Based on the existing data, we argue that SLN-mediated thermogenesis is an integral part of muscle NST and that muscle NST potentially contributed to the evolution of endothermy within the vertebrate clade. This article is part of the theme issue ‘Vertebrate palaeophysiology’.

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Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption

Cited by 84 publications

References 86 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

Thermogenesis in Adipose Tissue Activated by Thyroid Hormone

Uncoupling of sarcoendoplasmic reticulum calcium ATPase pump activity by sarcolipin as the basis for muscle non-shivering thermogenesis

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