scholarly journals Type-2 Iodothyronine 5′Deiodinase (D2) in Skeletal Muscle of C57Bl/6 Mice. II. Evidence for a Role of D2 in the Hypermetabolism of Thyroid Hormone Receptor α-Deficient Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3093-3102 ◽  
Author(s):  
W. Ramadan ◽  
A. Marsili ◽  
P. R. Larsen ◽  
A. M. Zavacki ◽  
J. E. Silva
Keyword(s):  
Skeletal Muscle ◽  
Nervous System ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Wild Type ◽  
High Fat ◽  
Consistent Finding ◽  
Alternate Form ◽  
Sympathetic Nervous

Mice with ablation of the Thra gene have cold intolerance due to an as yet undefined defect in the activation of brown adipose tissue (BAT) uncoupling protein (UCP). They develop an alternate form of facultative thermogenesis, activated at temperatures below thermoneutrality and associated with hypermetabolism and reduced sensitivity to diet-induced obesity. A consistent finding in Thra-0/0 mice is increased type-2 iodothyronine deiodinase (D2) mRNA in skeletal muscle and other tissues. With an improved assay to measure D2 activity, we show here that this enzyme activity is increased in proportion to the mRNA and as a function of the ambient cold. The activation is mediated by the sympathetic nervous system in Thra-0/0, as it is in wild-type genotype mice, but the sympathetic nervous system effect is greater in Thra-0/0 mice. Using D2-ablated mice (Dio2−/−), we reported elsewhere and show here that, in spite of sharing a severe deficiency in BAT thermogenesis with Thra-0/0 and UCP1-knockout mice, they do not have an increase in oxygen consumption, and they gain more weight than wild-type controls when fed a high-fat diet. UCP3 mRNA is highly responsive to thyroid hormone, and it is increased in Thra-0/0 mice, particularly when fed high-fat diets. We show here that muscle UCP3 mRNA in hypothyroid Thra-0/0 mice is responsive to small dose-short regimens of T4, indicating a role for locally, D2-generated T3. Lastly, we show that bile acids stimulate not only BAT but also muscle D2 activity, and this is associated with stimulation of muscle UCP3 mRNA expression provided T4 is present. These observations strongly support the concept that enhanced D2 activity in Thra-0/0 plays a critical role in their alternate form of facultative thermogenesis, stimulating increased fat oxidation by increasing local T3 generation in skeletal muscle.

scholarly journals Leptin Enhances Insulin Sensitivity by Direct and Sympathetic Nervous System Regulation of Muscle IGFBP-2 Expression: Evidence From Nonrodent Models

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2133-2143 ◽  
Author(s):  
Steven W. Yau ◽  
Belinda A. Henry ◽  
Vincenzo C. Russo ◽  
Glenn K. McConell ◽  
Iain J. Clarke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Nervous System ◽  
Insulin Sensitivity ◽  
Sympathetic Nervous System ◽  
Insulin Signaling ◽  
In Vivo Experiments ◽  
Sympathetic Nervous

Leptin is produced from white adipose tissue and acts primarily to regulate energy balance. Obesity is associated with leptin resistance and increased circulating levels of leptin. Leptin has recently been shown to influence levels of IGF binding protein-2 (IGFBP-2), a protein that is reduced in obesity and type 2 diabetes. Overexpression of IGFBP-2 protects against obesity and type 2 diabetes. As such, IGFBP-2 signaling may represent a novel pathway by which leptin regulates insulin sensitivity. We sought to investigate how leptin regulates skeletal muscle IGFBP-2 levels and to assess the impact of this on insulin signaling and glucose uptake. In vitro experiments were undertaken in cultured human skeletal myotubes, whereas in vivo experiments assessed the effect of intracerebroventricular leptin on peripheral skeletal muscle IGFBP-2 expression and insulin sensitivity in sheep. Leptin directly increased IGFBP-2 mRNA and protein in human skeletal muscle through both signal transducer and activator of transcription-3 and phosphatidylinositol 3-kinase signaling, in parallel with enhanced insulin signaling. Silencing IGFBP-2 lowered leptin- and insulin-stimulated protein kinase B phosphorylation and glucose uptake. In in vivo experiments, intracerebroventricular leptin significantly increased hind-limb skeletal muscle IGFBP-2, an effect completely blocked by concurrent peripheral infusion of a β-adrenergic blocking agent. Sheep receiving central leptin showed improvements in glucose tolerance and circulating insulin levels after an iv glucose load. In summary, leptin regulates skeletal muscle IGFBP-2 by both direct peripheral and central (via the sympathetic nervous system) mechanisms, and these likely impact on peripheral insulin sensitivity and glucose metabolism.

Thyroid hormone-catecholamine interrelationships during exposure to cold

1981 ◽  
Vol 97 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. Storm ◽  
C. van Hardeveld ◽  
A. A. H. Kassenaar
Keyword(s):  
Nervous System ◽  
Plasma Concentration ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Plasma Levels ◽  
Surgical Procedure ◽  
Exposure To Cold ◽  
Basal Plasma ◽  
Sympathetic Nervous

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.

Regulation of brown adipose tissue lipogenesis by thyroid hormone and the sympathetic nervous system

1993 ◽  
Vol 265 (2) ◽  
pp. E252-E258 ◽  
Author(s):  
W. J. Yeh ◽  
P. Leahy ◽  
H. C. Freake
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Northern Analysis ◽  
Brown Adipose ◽  
Sympathetic Nervous

Thyroid hormone regulates lipogenesis differently in rat liver and brown adipose tissue (BAT). In the hypothyroid state, lipogenesis is suppressed in liver but enhanced in BAT. Here we investigated the mechanisms underlying increased lipogenesis in hypothyroid BAT. Housing the animals at 28 degrees C decreased lipogenesis in hypothyroid BAT to euthyroid levels. Denervation resulted in a 90% reduction in lipogenesis in hypothyroid BAT such that levels were lower than in euthyroid tissue. Thyroid hormone treatment of hypothyroid rats stimulated fatty acid synthesis in denervated BAT, as in liver, but decreased it in intact BAT. Steady-state levels of mRNA encoding acetyl-CoA carboxylase, fatty-acid synthase, and spor 14 were measured in similar animals by Northern analysis. The expression of these mRNAs mirrored the lipogenic data, showing that both thyroid hormone and the sympathetic nervous system work at a pretranslational level in this tissue. These data suggest that the increased BAT lipogenesis found with hypothyroidism is mediated by the sympathetic nervous system to counter the reduction in metabolic rate in these animals.

scholarly journals Effect of aging on rat skeletal muscle beta-AR function in male Fischer 344 x brown Norway rats

1996 ◽  
Vol 270 (2) ◽  
pp. R462-R468 ◽  
Author(s):  
L. M. Larkin ◽  
J. B. Halter ◽  
M. A. Supiano
Keyword(s):  
Skeletal Muscle ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Muscle ◽  
Brown Norway ◽  
Sympathetic Nervous System Activity ◽  
System Activity ◽  
Fischer 344 ◽  
Nervous System Activity ◽  
Sympathetic Nervous

In this study, we tested the hypothesis that, in the male Fischer 344 x Brown Norway (F344xBN) rat, aging would be associated with an increase in sympathetic nervous system activity and a decrease in skeletal muscle beta-adrenergic-receptor (beta-AR) density and function. Radioligand-binding studies using [125I] iodocyanopindolol were done to evaluate beta-AR density (Bmax) and antagonist-binding affinity in gastrocnemius and cardiac muscle from 6-, 18-, and 28-mo-old male F344xBN rats. beta-AR function was measured as adenylyl cyclase (AC) activity stimulated by the beta-AR agonist isoproterenol (Iso, 10(-4) M). Basal arterial plasma norepinephrine (pNE) concentrations were higher in the 28-than in the 6- and 18-mo-old rats. Bmax was greatest and Iso-stimulated AC activity was unchanged in gastrocnemius muscle of the 28-mo-old age group. In contrast, there was an age-associated decrease in Bmax and Iso-stimulated AC activity in cardiac muscle. In conclusion, there was an age-associated increase in pNE concentrations in male F344xBN rats, suggesting an increase in sympathetic nervous system activity. In addition, there was an age-associated increase in skeletal muscle beta-AR density, whereas in skeletal muscle beta-AR-stimulated AC activity remained unchanged with age.

Influence of the Sympathetic Nervous System on the Secretion and Metabolism of Thyroid Hormone

Endocrinology ◽  
1977 ◽  
Vol 101 (4) ◽  
pp. 1228-1237 ◽  
Author(s):  
A. MELANDER ◽  
U. WESTGREN ◽  
L. E. ERICSON ◽  
F. SUNDLER
Keyword(s):  
Nervous System ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Sympathetic Nervous

scholarly journals Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Doyeon Kim ◽  
Yuna Lee ◽  
Hyeung-Rak Kim ◽  
Yeo Jin Park ◽  
Hongik Hwang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Signaling Pathways ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Sympathetic Nervous

AbstractSargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

scholarly journals Relationships of Adrenoceptor Polymorphisms with Obesity

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Kazuko Masuo ◽  
Gavin W. Lambert
Keyword(s):  
Type 2 Diabetes ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Reactivity ◽  
Nervous Activity ◽  
Epidemiological Studies ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous ◽  
Obesity Hypertension

Obesity, hypertension, and type 2 diabetes are rapidly growing public health problems. Heightened sympathetic nerve activity is a well-established observation in obesity, hypertension, and type 2 diabetes. Human obesity, hypertension, and diabetes have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity are mainly mediated via the β2, and β3-adrenergic receptors in humans. Further, β2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. β-adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic nervous activity. Many epidemiological studies have shown strong relationships between adrenoceptor polymorphisms and obesity, but the observations have been discordant. This paper will discuss the current topics involving the influence of the sympathetic nervous system and β2- and β3-adrenoceptor polymorphisms in obesity.

scholarly journals Roles of Beta2- and Beta3-Adrenoceptor Polymorphisms in Hypertension and Metabolic Syndrome

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Kazuko Masuo
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Reactivity ◽  
Resting Metabolic Rate ◽  
Sympathetic Nervous ◽  
Obesity Hypertension ◽  
Sympathetic Nerve Activation

Hypertension, diabetes mellitus (especially type 2 diabetes mellitus), metabolic syndrome and obesity are rapidly growing public health problems. Sympathetic nerve activation is observed in obesity, hypertension and diabetes mellitus, which have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the 2- and 3-adrenergic receptors in humans. Further, 2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the -adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. 2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile) have been studied in relation to hypertension. Genetic variations in the 3-adrenoceptor (i.e. Try64Arg variant) are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of 2- and 3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and 2- and 3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.

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