A model for chronic, intrahypothalamic thyroid hormone administration in rats

Zhi, Zhang; Bisschop, Peter H.; Foppen, Ewout; Beeren, H C van; Kalsbeek, Andries; Boelen, Anita; Fliers, Eric

doi:10.1530/joe-15-0501

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…As expected, after placement of T3-containing pellets in the PVN, plasma T3 and T4 decreased, while there was no change in plasma TH after placement of T3-containing pellets in the VMH. Thus, our model is valid to selectively and chronically deliver T3 to specific hypothalamic nuclei [76]. However, surprisingly, body weight, food intake, and body temperature were not changed after T3 administration in the PVN or VMH for 28 days despite these nuclei-specific changes.…”

Section: Systemic Effects Of Intrahypothalamic Thmentioning

confidence: 97%

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: Systemic Effects Of Intrahypothalamic Thmentioning

confidence: 97%

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

Zhi¹,

Boelen²,

Kalsbeek³

et al. 2018

Eur Thyroid J

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“…ELISA Serum levels of tT4 (EIA-1781, DRG Diagnostics, Germany) and tT3 (DNOV053, NovaTec Immundiagnostica GmbH, Germany) were determined according to manufacturer's instructions. Hypothalamic T3 content was measured in pooled hypothalamic punches of the lateral and basal hypothalamus as described previously (Zhang et al, 2016). cAMP levels in ingWAT and iBAT were determined according to manufacturer's instructions (RPN225, GE Healthcare, UK).…”

Section: Enzyme Activity and Glycogen Measurementmentioning

confidence: 99%

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

et al. 2019

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“…Therefore, while elevated T3 increases food intake in an acute setting, this may not occur with chronic elevation. Indeed, differing acute and chronic effects of T3 were observed in other hypothalamic nuclei, as acute [54] but not chronic [55], delivery of T3 into the PVN raised blood glucose levels.…”

Section: Discussionmentioning

confidence: 99%

Global transcriptomic analysis of the arcuate nucleus following chronic glucocorticoid treatment

Wray

Davies

Sefton

et al. 2019

Molecular Metabolism

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Objective Glucocorticoids (GCs) are widely prescribed medications that are well recognized to cause adverse metabolic effects including hyperphagia, obesity, and hyperglycemia. These effects have been recapitulated in a murine model of GC excess, and we hypothesize that they are mediated, in part, through central mechanisms. This study aimed to identify genes in the hypothalamic arcuate nucleus (ARC) that are altered with GC treatment and evaluate their contribution to GC-induced metabolic abnormalities. Methods Corticosterone (Cort; 75 μg/ml) was administered in the drinking water to male C57Bl/6J mice for 2 days or 4 weeks. Phenotypic analysis of each group was undertaken and central and peripheral tissues were collected for biochemical and mRNA analyses. Arcuate nuclei were isolated by laser capture microdissection and tissue analyzed by RNA-seq. Results RNA-seq analysis of ARC tissue from 4 week Cort treated mice revealed 21 upregulated and 22 downregulated genes at a time when mice had increased food intake, expansion of adipose tissue mass, and insulin resistance. In comparison, after 2 days Cort treatment, when the main phenotypic change was increased food intake, RNA-seq identified 30 upregulated and 16 downregulated genes. Within the genes altered at 2 days were a range of novel genes but also those known to be regulated by GCs, including Fkbp5 , Mt2 , Fam107a , as well as some involved in the control of energy balance, such as Agrp , Sepp1 , Dio2 , and Nmb . Of the candidate genes identified by RNA-seq, type-II iodothyronine deiodinase ( Dio2 ) was chosen for further investigation as it was increased (2-fold) with Cort, and has been implicated in the control of energy balance via the modulation of hypothalamic thyroid hormone availability. Targeted knockdown of Dio2 in the MBH using AAV-mediated CRISPR-Cas9 produced a mild attenuation in GC-induced brown adipose tissue weight gain, as well as a 56% reduction in the GC-induced increase in Agrp . However, this conferred no protection from GC-induced hyperphagia, obesity, or hyperglycemia. Conclusions This study identified a comprehensive set of genes altered by GCs in the ARC and enabled the selection of key candidate genes. Targeted knockdown of hypothalamic Dio2 revealed that it did not mediate the chronic GC effects on hyperphagia and hyperglycemia.

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A model for chronic, intrahypothalamic thyroid hormone administration in rats

Cited by 9 publications

References 30 publications

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

TRH Neurons and Thyroid Hormone Coordinate the Hypothalamic Response to Cold

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

Global transcriptomic analysis of the arcuate nucleus following chronic glucocorticoid treatment

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