The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

Hofer, Doris; Raı́ces, Marcela; Schauenstein, Konrad; Porta, S.; Korsatko, W.; Hagmüller, K.; Zaninovich, Angel A.

doi:10.1530/eje.0.1430273

Cited by 4 publications

(2 citation statements)

References 22 publications

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“…Numerous complex phenomena take place in BAT after exposure to low temperatures, leading to the synthesis of mitochondrial proteins involved in heat production. A critical role in this process is the synthesis of uncoupling protein-1 (UCP-1), strongly promoted by norepinephrine (NE) through a synergism between ␣-and ␤-adrenergic receptors (24,32,40). The presence of the thyroid hormones is essential to initiate BAT heat production, because triiodothyronine (T 3 ) potentiates the action of NE on UCP-1 gene transcription (2-4, 37).…”

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confidence: 99%

Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

Zaninovich¹,

Raı́ces

Rebagliati³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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-The effects of long-term cold exposure on brown adipose tissue (BAT) thermogenesis in hypothyroid rats have been examined. Thyroid ablation was performed in normal rats after 2 mo of exposure to 4°C, when BAT hypertrophy and thermogenic activity were maximal. After ablation, hypothyroid and normal controls remained in the cold for 2 additional months. At the end of the 4-mo cold exposure, all untreated hypothyroid rats were alive, had normal body temperature, and had gained an average 12.8% more weight than normal controls. Long-term cold exposure of hypothyroid rats markedly increased BAT weight, mitochondrial proteins, uncoupling protein (UCP)-1, mRNA for UCP-1, and oxygen consumption to levels similar to those seen in cold-exposed normal rats. The results indicate that thyroid hormones are required for increased thermogenic capacity to occur as an adaptation to long-term cold exposure. However, cold adaptation can be maintained in the absence of thyroid hormone. cold acclimation; uncoupling protein-1; hypothyroidism; oxygen consumption; norepinephrine THE IMPORTANCE OF THE BROWN ADIPOSE TISSUE (BAT) thermogenic response to acute cold stress has been widely recognized (for reviews see Refs. 21,22,30). Numerous complex phenomena take place in BAT after exposure to low temperatures, leading to the synthesis of mitochondrial proteins involved in heat production. A critical role in this process is the synthesis of uncoupling protein-1 (UCP-1), strongly promoted by norepinephrine (NE) through a synergism between ␣-and ␤-adrenergic receptors (24,32,40). The presence of the thyroid hormones is essential to initiate BAT heat production, because triiodothyronine (T 3 ) potentiates the action of NE on UCP-1 gene transcription (2-4, 37). This explains the development of hypothermia in hypothyroid rats soon after exposure to low temperatures, an effect corrected by the administration of thyroid hormones but not by the administration of NE (39).Thyroid hormones are active regulators of basal metabolic rate (BMR) and energy expenditure by a number of mechanisms (9,12,38,39). However, earlier studies had suggested that the thyroid hormone may not be necessary for a sustained normothermia after acclimation to cold has been achieved (for review see Ref. 13). Thus Hsieh and Carlson (25) observed a high metabolic rate and normal life survival in hypothyroid rats adapted to cold before thyroidectomy. Despite numerous studies, the influence of thyroid function on the maintenance of normothermia in rodents exposed to prolonged low temperature is not clearly understood.The purpose of the present study was to assess the role of the thyroid hormones in BAT thermogenesis during long-term cold exposure. After a period of time in the cold, rats were made hypothyroid. Hypothyroid and normal controls were then maintained for an additional period of time in the cold, and thereafter BAT was studied. Accordingly, hypothyroidism was induced after BAT hypertrophy and thermogenic activity were maximally activated. In contrast, room temperaturea...

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confidence: 99%

Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

Zaninovich¹,

Raı́ces

Rebagliati³

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…A recent study [102] has demonstrated the unexpected presence of TSH receptors in human abdominal WAT although their functional relevance here is not yet understood. The SNS not only influences the tissue effects of thyroid hormones via effects on the de-iodination of T4 to the more potent T3 [103,104] but also by modifica-tion of the effects of thyroid hormones on mRNA transcriptional activity, at least in rodent BAT [1051. Conversely, thyroid hormones can regulate adenyl cyclase activity in rodent BAT [106] and a state of hypothyroidism leads to differential Il-adrenoceptor expression as well as post-receptor effects in both the brown and white AT of rats [107].…”

Section: Human Studies-limitations and Resultsmentioning

confidence: 99%

The Endocrine Function of the Fat Cell-Regulation by the Sympathetic Nervous System

Vj¹,

Sw²

2000

Horm Metab Res

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The landmark discovery of leptin established beyond question the fact that adipose tissue is a crucial active regulator of body weight, an endocrine organ in its own right and part of a feedback circuit possessing both afferent and efferent loops. This is in addition to its more established roles as a receiver of incoming endocrine signals and modulator of circulating hormones such as sex steroids. Since this discovery, much has been learned about the role of leptin in the afferent loop of the hypothalamic regulation of body weight and indeed about some of the neuro-endocrine circuitry involved in the regulation of appetite and weight. Much less, however, is known about the efferent limb of the circuit, specifically relating to how the hypothalamus is able to influence adipocyte behaviour and how this link may itself be influenced by endocrine and paracrine signals, both acting on and emanating from adipocytes themselves, acting at multiple levels. This review will focus on the role of the sympathetic nervous system (SNS) and adreno-medullary system in relation to the regulation of adipose tissue physiology and endocrine function. The evidence in support of the hypothesis that the SNS is a crucial mediator of the efferent loop of this feedback circuit will be considered.

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Thermogenesis and Related Metabolic Targets in Anti-Diabetic Therapy

Arch

2011

Diabetes - Perspectives in Drug Therapy

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Exercise, together with a low-energy diet, is the first-line treatment for type 2 diabetes type 2 diabetes . Exercise improves insulin sensitivity insulin sensitivity by increasing the number or function of muscle mitochondria mitochondria and the capacity for aerobic metabolism, all of which are low in many insulin-resistant subjects. Cannabinoid 1-receptor antagonists and β-adrenoceptor agonists improve insulin sensitivity in humans and promote fat oxidation in rodents independently of reduced food intake. Current drugs for the treatment of diabetes are not, however, noted for their ability to increase fat oxidation, although the thiazolidinediones increase the capacity for fat oxidation in skeletal muscle, whilst paradoxically increasing weight gain.There are a number of targets for anti-diabetic drugs that may improve insulin sensitivity insulin sensitivity by increasing the capacity for fat oxidation. Their mechanisms of action are linked, notably through AMP-activated protein kinase, adiponectin, and the sympathetic nervous system. If ligands for these targets have obvious acute thermogenic activity, it is often because they increase sympathetic activity. This promotes fuel mobilisation, as well as fuel oxidation. When thermogenesis thermogenesis is not obvious, researchers often argue that it has occurred by using the inappropriate device of treating animals for days or weeks until there is weight (mainly fat) loss and then expressing energy expenditure energy expenditure relative to body weight. In reality, thermogenesis may have occurred, but it is too small to detect, and this device distracts us from really appreciating why insulin sensitivity has improved. This is that by increasing fatty acid oxidation fatty acid oxidation more than fatty acid supply, drugs lower the concentrations of fatty acid metabolites that cause insulin resistance. Insulin sensitivity improves long before any anti-obesity effect can be detected.

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The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine deiodination in cold-exposed, sympathectomized rat brown fat

Cited by 4 publications

References 22 publications

Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

Brown fat thermogenesis in cold-acclimated rats is not abolished by the suppression of thyroid function

The Endocrine Function of the Fat Cell-Regulation by the Sympathetic Nervous System

Thermogenesis and Related Metabolic Targets in Anti-Diabetic Therapy

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