Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice

Weiner, Juliane; Kranz, Mathias; Klöting, Nora; Kunath, Anne; Steinhoff, Karen Geva; Rijntjes, Eddy; Köhrle, Josef; Zeisig, Vilia; Hankir, Mohammed K.; Gebhardt, Claudia; Deuther‐Conrad, Winnie; Heiker, John T.; Kralisch, Susan; Stümvoll, Michael; Blüher, Matthias; Sabri, Osama; Hesse, Swen; Brust, Peter; Tönjes, Anke; Krause, Kerstin

doi:10.1038/srep38124

Cited by 78 publications

(82 citation statements)

References 51 publications

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“…Together these studies indicate an important role for TH regulation of WAT thermogenesis during cold exposure. However, another recent study paradoxically showed that both hyperthyroidism and hypothyroidism increased WAT browning in mice [38]. Since the hypothyroid mice showed reduced BAT activity, the authors hypothesized compensatory WAT browning in response to decreased heat production due to BAT inactivity, as suggested previously by others [39].…”

Section: Effects Of Th On Adaptive Thermogenesis and Heat Conservationsupporting

confidence: 49%

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

Zhi¹,

Boelen²,

Kalsbeek³

et al. 2018

Eur Thyroid J

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Thyroid hormone (TH) plays a key role in regulating body temperature in mammals. Cold exposure stimulates the hypothalamus-pituitary-thyroid (HPT) axis at the hypothalamic level by activating hypophysiotropic thyrotropin-releasing hormone (TRH)-producing neurons, ultimately resulting in increased plasma TH concentrations. Importantly, the local TH metabolism within various cold-responsive organs enables tissue-specific action of TH on heat production and adaption to cold independently of the circulating TH levels. In addition to these neuroendocrine effects, TRH neurons in the hypothalamus also have neural connections with brown adipose tissue (BAT), probably contributing to regulation of thermogenesis by the autonomic nervous system. Recent studies have demonstrated that intrahypothalamic TH has profound metabolic effects on BAT, the liver, and the heart that are mediated via the autonomic nervous system. These effects originate in various hypothalamic nuclei, including the paraventricular nucleus (PVN), the ventromedial nucleus, and recently reported neurons in the anterior hypothalamic area, indicating a potential central function for TH on thermoregulation. Finally, although robust stimulation of the thermogenic program in BAT was shown upon TH administration in the ventromedial hypothalamus, the physiological relevance of these neurally mediated effects of TH is unclear at present. This review provides an overview of studies reporting the role of TH in cold defense, with a focus on recent literature evidencing the centrally mediated effects of TRH and TH.

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Section: Effects Of Th On Adaptive Thermogenesis and Heat Conservationsupporting

confidence: 49%

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

Zhi¹,

Boelen²,

Kalsbeek³

et al. 2018

Eur Thyroid J

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“…Fixed ganglia were washed in tris-PBS (TPBS) to remove fixative before being incubated in increasing concentrations of a fructose solution (20,40,60,80, and 100%) containing 0.5% a-thioglycerol for 6 h each. The tissues were then transferred, stored, and imaged in SeeDB solution [80.2 (w/w) fructose solution+0.5% a-thioglycerol].…”

Section: Determination Of the Total Number Of Prv Labeled Neurons In mentioning

confidence: 99%

Characterization of the central neural projections to brown, white, and beige adipose tissue

2017

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The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue.

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“…Primarily by hepatic action, thyroid hormone therapy can lower the circulating concentration of cholesterol and lipoproteins (Angelin and Rudling, 2010). In adipose depots, thyroid hormone can promote energy expenditure and lipolysis (Lin et al, 2015;Weiner et al, 2016). Central actions of thyroid hormone include hyperphagia and sympathetic outflow, which can also increase energy expenditure and cardiovascular adrenergic input (Lopez et al, 2010;Mittag et al, 2013).…”

Section: B Glucagon-mediated Delivery Of Thyroid Hormone Tri-iodothymentioning

confidence: 99%